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| 1 | Antimicrobial activity of Sapindus mukorossi and Rheum emodi extracts against H pylori: In vitro and in vivo studies显示文摘AIM: To evaluate the antibacterial activity of Sapindus mukorossi (S. mukorossi) and Rheum emodi (R. emodi). METHODS: Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzene, chloroform and ethanol and were concentrated in vacuum. The disk diffusion method was used for in vitro studies and in vivo studies were performed on male Wister rats. Thirty resistant clinical isolates of H pylori, as determined by their antibiotic sensitivity patterns by E-test, along with two Gram +ve (S. aureus, B. subtilis) and two Gram -ve (E. coli, P. vugaris) organisms were screened for their susceptibility patterns against these extracts. RESULTS: In our screening, all 30 resistant isolates and the other four organisms (two Gram +ve S. aureus, B. subtilis and two Gram -ve, E. coli, P. vugaris) were sensitive to the test compounds. It was found that ethanol and chloroform extracts of S. mukorossi and ethanol and benzene extracts of R. emodi inhibited H pylori at very low concentrations. In the in vitro study, the isolates showed a considerable zone of inhibition at very low concentrations (10 μg/mL) for both the extracts. In the in vivo study, the H pylori infection was cleared with minimal doses of extracts of S. mukorossi (2.5 mg/mL) and R. emodi (3.0 mg/mL) given orally for seven days. CONCLUSION: We can conclude from this study that the extracts of S. mukorossi and R. emodi inhibited the growth of pylori in vitro and, in in vivo studies, the H pylori infection cleared within seven days at very low concentrations. We also found that H pylori did not acquire resistance against these herbal extracts even after 10 consecutive passages. | Mohammed Ibrahim Aleem A Khan Santosh K Tiwari Mohammed Aejaz Habeeb MN Khaja CM Habibullah | 2006 | World Journal of Gastroenterology2006,12,44: | 46 |
| 2 | STAT6免疫组化染色有助于孤立性纤维性肿瘤的诊断显示文摘孤立性纤维性肿瘤(SFT)发生部位非常广泛,多数为良性,约10%的病例表现为侵袭性。根据组织学特征和CD34表达能够对大多数SYT病例做出准确诊断,但SFT组织学的多样性、偶尔出现意外的免疫表型可能对诊断造成困难。分子分析发现大多数良恶性SFTs均存在特异性NAB2-STAT6融合基因。但基因检测需要专门的设备,花费较高,无法常规应用。 | Yoshida A Tsuta K Ohno M 李慧明(摘译) 余英豪(审校) | 2014 | 临床与实验病理学杂志2014,30,5: | 41 |
| 3 | 患者肠道微生物群失调与肠上皮屏障功能障碍显示文摘最近的证据表明,在动物模型中,肠道病理学和微生物组与高血压之间存在联系。然而,这种关联在人类中是否存在尚不清楚。因此,该研究的目的是检验高血压患者具有明显特异的肠道微生物组以及肠上皮屏障功能标记物和微生物组组成可以预测收缩压变化的假设。研究者通过鸟枪法宏基因组学分析粪便样本显示微生物分类和功能变化,结果显示高血压患者和对照受试者之间丁酸盐产生存在差异。 | Kim S Goel R Kumar A Qi Y Lobaton G Hosaka K Mohammed M Handberg EM Richards EM Pepine CJ Raizada MK 刘青 叶鹏 | 2018 | 中华高血压杂志2018,26,9: | 45 |
| 4 | Analysis of the phosphatidylinosit ol 3'-kinase signaling pathway in glioblastoma patients in vivo显示文摘Deregulated signaling through the p hosphatidylinositol 3-kinase(PI3K)pathway is common in many types of can cer,including glioblastoma.Dissecting the molecular events associated with activation of this pathway in glioblastoma p atients in vivo presents an important challenge that has implic ations for the development and clini cal testing of PI3K pathway inhibito rs.Using an immunohistochemical analysis appl ied to a tissue microarray,we performed hierarchical clustering and mul tidimensional scaling,as well as univariate and multivariate analyses,to dissect the PI3K pathway in v ivo.We demonstrate that loss of the t umor suppressor protein PTEN,which antagonizes PI3K pathwa y activation,is highly correlated w ith activation of the main PI3K effec tor Akt in vivo.We also show that Akt activation is signific antly correlated with phosphorylation of mammalian target of rapamycin(mTOR),the family of forkhead transcription factors(FOXO1,FOXO3a,and FOXO4),and S6,which are thought to promote its effects.Expression of the mutan t epidermal growth factor receptor vIII is also tightly correlated with phosphorylation of these effectors,d emonstrating an additional route to PI3K pathway activation in glioblastomas in vivo.These results provide the first dissection of the PI3K path way in glioblastoma in vivo and suggest an approach to stratifying patients for targeted kinase inhi bitor | Choe G Horvath S Cloughesy TF Crosby K Seligson D Palotie A Inge L Smith BL Sawyers CL Mischel PS | 2003 | 癌症2003,22,7: | 41 |
| 5 | Treatment options for alcoholic and non-alcoholic fatty liver disease: A review显示文摘Alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma.Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver(simple steatosis),a small percentage develops progressive liver disease.Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available.The treatment for ALD remains as it was 50 years ago:abstinence,nutritional support and corticosteroids(or pentoxifylline as an alternative if steroids are contraindicated).As for NAFLD,the treatment modality is mainly directed toward weight loss and co-morbidity management.Therefore,new pathophysiology directed therapies are urgently needed.However,the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy.Hence,a combination therapy towards multiple targets would eventually be required.In this review,we delineate the treatment options in ALD and NAFLD,including various new targeted therapies that are currently under investigation.We hope that soon we will be having an effective multi-therapeutic regimen for each disease. | Sukhpreet Singh Natalia A Osna Kusum K Kharbanda | 2017 | World Journal of Gastroenterology2017,23,36: | 45 |
| 6 | Adult neural stem cells in the mammalian central nervous system显示文摘神经干细胞(NSC ) 不仅在胚胎的发展期间而且在所有哺乳动物的种类的成年大脑是在场的,包括人。在 vivo 的干细胞壁龛建筑学使成年 NSC 能连续地在整个生活在特定的大脑区域产生功能的神经原。成年神经发生过程服从于动态规定由各种各样生理,病理学并且药理学刺激。Multipotent 成年 NSC 也看起来内在地塑料,对基因编程顺从在正常区别期间,并且到 epigenetic reprograming 在进 pluripotency 的 de 区别期间。增加的证据建议成年 NSC 显著地在生理、病理学的条件下面贡献专业化神经功能。充分理解成年 NSC 的生物学将提供关键卓见进病原学和主要大脑混乱的潜在的治疗学的干预。这里,我们在哺乳动物的中央神经系统的成年 NSC 上考察最近的进步,包括他们在癌症和再生药的身份,壁龛,功能,粘性,和新兴的角色上的话题。 | Dengke K Ma | 2009 | Cell Research2009,19,6: | 35 |
| 7 | AGNP精神科治疗药物监测共识指南:2011显示文摘治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从'强烈推荐'到'可能有用'的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的'治疗参考浓度范围'和'剂量相关参考浓度范围'呈现给大家。本共识指南引入了'实验室警戒浓度'的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中获益。 | Hiemke C Baumann P Bergemann N Conca A Dietmaier O Egberts K Fric M Gerlach M Greiner C Gründer G Haen E Havemann-Reinecke U Jaquenoud Sirot E Kirchherr H Laux G Lutz UC Messer T Müller MJ Pfuhlmann B Rambeck B Riederer P Schoppek B Stingl J Uhr M Ulrich S Waschgler R Zernig G 李文标(译) 果伟(译) 阮灿军(译) 贺静(译) 汤宜朗(审校) 王传跃(审校) | 2016 | 实用药物与临床2016,19,10: | 37 |
| 8 | 文献快报(8):芬兰学龄前儿童抗生素使用与其肠道菌群的相关性研究显示文摘有研究表明,早期抗生素的使用增加了儿童肠炎、超重和哮喘的风险。成人试验研究表明,口服抗生素能明显改变肠道微生物菌群,减少菌群的多样性,改变菌群的构成,但其样本量非常有限。在新生儿中使用抗生素治疗者和未使用抗生素治疗者其体内肠道微生物菌群存在较大差异,但至今尚不清楚早期使用抗生素对儿童肠道微生物菌群的远期影响。 | korpela k salonen a virta l j 苏普玉(译) | 2016 | 中国学校卫生2016,37,8: | 31 |
| 9 | 新媒体联盟地平线报告:2017图书馆版显示文摘地平线报告系列展示了5年内创新实践和技术对全球学术与研究型图书馆的影响。报告涉及6大关键趋势,6种重要挑战和6项技术发展,它们影响着图书馆战略、运营和服务,包括学习、创意调查、研究和信息管理。其中专家们认为大数据、数字学术技术、图书馆服务平台、网络身份、人工智能、物联网等技术具有促进学术和研究型图书馆发生真正改变的潜力。本报告为图书馆领导者、图书馆工作人员、政策制定者和技术人员提供参考和技术规划指南。 | S·亚当斯·贝克尔 M·卡明斯 A·戴维斯 A·弗里曼 C·霍尔·盖辛格 V·安娜塔娜额亚娟 K·兰利 N·沃尔夫森 高茜(译) 曹红岩(译) 徐路(译) 周晖(译) 谢艳秋(译) 洪长勇(译) 王丽媛(译) 鄂丽君(译) | 2017 | 开放学习研究2017,22,5: | 33 |
| 10 | 最新AD研究用诊断标准:IWG-2标准显示文摘在过去的8年中,国际工作组织(IWG)和美国国立老化研究院-阿尔茨海默协会(NIA-AA)建立了阿尔茨海默病(AD)诊断标准,它能更好地定义AD的临床表型,整合了生物标记物于诊断流程中,并覆盖了疾病的全程。本意见书充分地权衡了IWG标准的优缺点,建议改进诊断框架。依据这些改进,AD的诊断变得简单,只要有恰当的AD临床表型(典型或不典型)和与AD的病理相一致的病理生理学生物标志物出现。我们认为疾病的下游的定位性生物标志,如容积性磁共振成像(MRI)和氟脱氧葡萄糖-正电子发射型计算机断层成像(FDG-PET)等,适合更好地测量和监测疾病过程。本文还详述了非典型性AD、混合性AD和AD临床前期的特异诊断标准。 | 陈刚 曹雯炜 俞羚 糜建华 Dubois B Feldman HH Jacova C Hampel H Molinuevo JL Blennow K DeK osky ST Gauthier S Selkoe D Bateman R Cappa S Crutch S Engelborghs S Frisoni GB Fox NC Galasko D Habert MO Jicha GA Nordberg A Pasquier F Rabinovici G Robert P Rowe C Salloway S Sarazin M Epelbaum S de Souza LC Vellas B Visser PJ Schneider L Stern Y Scheltens P Cummings JL | 2014 | 神经病学与神经康复学杂志2014,11,3: | 31 |
| 11 | 尿钠排泄、血压、心血管病与死亡率的关系:社区前瞻性流行病学队列研究显示文摘WHO建议人群钠摄人<2 g/d作为预防心血管病的措施之一,但这一目标在任何国家都没有实现。该建议主要基于短期血压试验的个体水平数据,没有来自随机试验或观察性研究的关于低钠摄入与降低心血管事件的数据。前瞻性城市农村流行病学研究目前正在21个国家进行。该文对其中18个国家的数据进行分析,其中包含了临床结果数据。 | Mente A O'Donnell M Rangarajan S McQueen M Dagenais G Wielgosz A Lear S Ah STL Wei L Diaz R Avezum A Lopez-Jaramillo P Lanas F Mony P Szuba A Iqbal R Yusuf R Mohammadifard N Khatib R Yusoff K Ismail N Gulec S Rosengren A Yusufali A Kruger L Tsolekile LP Chifamba J Dans A Alhabib KF Yeates K Teo K Yusuf S 刘莉 叶鹏 | 2018 | 中华高血压杂志2018,26,12: | 29 |
| 12 | 高地应力特厚煤层“蠕变型”冲击机理研究显示文摘多起'蠕变型'冲击事故分析表明:该类冲击属于典型的隐蔽性灾害,具有自发性和时滞性的特点,发生机理的不明导致其防治极具挑战,给深部特厚煤层的安全开采造成了严重威胁。'蠕变型'冲击与不稳定蠕变密切相关,通过建立蠕变模型和三维蠕变方程,得到高地应力与特厚煤层为不稳定蠕变的形成提供了有利的孕育条件;分析了巷道围岩不稳定蠕变破坏的过程,认为不稳定蠕变通过强度'腐蚀'和应力解除2方面实现启动冲击和减小阻抗,从而在受外部静态应力叠加影响的巷道薄弱区域形成'蠕变型'冲击,并提出了判别其发生可能性的评估公式。针对这类冲击的发生机理,提出了针对性的防治措施建议:合理布置巷道、加强主动支护、优化卸压参数和长期监测。 | 姜福兴 | 2015 | 岩土工程学报2015,37,10: | 30 |
| 13 | 急性缺血性卒中的血管内治疗:神经介入外科学学会实践标准委员会的报告显示文摘目的总结采用血管内技术治疗急性缺血性卒中的有关证据并等级分类。方法对美国心脏协会(American Heart Association,AHA)以前发表的推荐意见进行审查并作为当前流程的基础。在此这基础上,进行系统的文献回顾以评估支持急性缺血性卒中血管内治疗的证据。根据AHA卒中委员会和牛津大学循证医学中心提出的循证医学证据分级指南进行评估。对操作安全性、技术效果以及对临床转归的影响进行特别审核。 | K A Blackham P M Meyers T A Abruzzo F C Alberquerque D Fiorella J Fraser D Frei C D Gandhi D V Heck J A Hirsch D P Hsu M Jayaraman S Narayanan C Prestigiacomo J L Sunshine 包元飞(译) 李永坤(译) 刘新峰(译) | 2012 | 国际脑血管病杂志2012,20,12: | 28 |
| 14 | History of the infantile hepatic hemangioma:From imaging to generating a differential diagnosis显示文摘We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed articles on hepatic infantile hemangiomas,published between 2000 and 2015,were reviewed for this study.IHH is the most common hepatic vascular tumor in children.Once a liver mass is identified in an infant,the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma,hepatoblastoma,metastatic neuroblastoma,so careful physical examination,imaging studies,and,if indicated,tumor markers and biopsy,are of pivotal importance to ascertain the correct diagnosis.Despite the benign nature of IHHs,some of these lesions may demand medical and/or surgical intervention,especially for multiple and diffuse IHH.Complications can include hepatomegaly,hypothyroidism and cardiac failure.Therefore,a close follow-up is required until complete involution of the lesions.We propose an algorithm to guide the physicians towards the proper management of hepatic lesions. | Maria Gnarra Gerald Behr Alison Kitajewski June K Wu Sudha A Anupindi Carrie J Shawber Nick Zavras Dimitrios Schizas Chris Salakos Konstantinos P Economopoulos | 2016 | World Journal of Clinical Pediatrics2016,5,3: | 27 |
| 15 | Global burden, distribution, and interventions for infectious diseases of poverty显示文摘Infectious diseases of poverty(IDoP)disproportionately affect the poorest population in the world and contribute to a cycle of poverty as a result of decreased productivity ensuing from long-term illness,disability,and social stigma.In 2010,the global deaths from HIV/AIDS have increased to 1.5 million and malaria mortality rose to 1.17 million.Mortality from neglected tropical diseases rose to 152,000,while tuberculosis killed 1.2 million people that same year.Substantial regional variations exist in the distribution of these diseases as they are primarily concentrated in rural areas of Sub-Saharan Africa,Asia,and Latin America,with geographic overlap and high levels of co-infection.Evidence-based interventions exist to prevent and control these diseases,however,the coverage still remains low with an emerging challenge of antimicrobial resistance.Therefore,community-based delivery platforms are increasingly being advocated to ensure sustainability and combat co-infections.Because of the high morbidity and mortality burden of these diseases,especially in resource-poor settings,it is imperative to conduct a systematic review to identify strategies to prevent and control these diseases.Therefore,we attempted to evaluate the effectiveness of one of these strategies,that is community-based delivery for the prevention and treatment of IDoP.In this paper,we describe the burden,epidemiology,and potential interventions for IDoP.In subsequent papers of this series,we describe the analytical framework and the methodology used to guide the systematic reviews,and report the findings and interpretations of our analyses of the impact of community-based strategies on individual IDoPs. | Zulfiqar A Bhutta Johannes Sommerfeld Zohra S Lassi Rehana A Salam Jai K Das | 2014 | Infectious Diseases of Poverty2014,3,1: | 21 |
| 16 | 日本人未破裂脑动脉瘤出血的危险性:对日本医生发表文献的系统研究显示文摘 | Morita A Fujiwara S Hashi K 赵刚 | 2005 | 中国微侵袭神经外科杂志2005,10,7: | 20 |
| 17 | Rare Earths and Magnetic Refrigeration显示文摘Magnetic refrigeration is a revolutionary, efficient, environmentally friendly cooling technology, which is on the threshold of commercialization. The magnetic rare earth materials are utilized as the magnetic refrigerants in most cooling devices, and for many cooling application the Nd2Fe 14 B permanent magnets are employed as the source of the magnetic field. The status of the near room temperature magnetic cooling was reviewed. | Karl A Gschneidner Vitalij K Pecharsky | 2006 | Journal of Rare Earths2006,24,6: | 20 |
| 18 | Modified porous tantalum rod technique for the treatment of femoral head osteonecrosis显示文摘AIM: To study a modified porous tantalum technique for the treatment of osteonecrosis of the femoral head.METHODS: The porous tantalum rod was combined with endoscopy,curettage,autologous bone grafting and use of bone marrow aspirates from iliac crest aspiration in 49 patients(58 hips) with a mean age of 38 years.The majority of the patients had idiopathic osteonecrosis,followed by corticosteroid-induced osteonecrosis.Thirtyeight hips were of Steinberg stage Ⅱ disease and 20 hips were of stage Ⅲ disease.Patients were followed for 5 years and were evaluated clinically with the Merle D'Aubigne and Postel score and radiologically.The primary outcome of the study was survival based on the conversion to total hip arthroplasty(THA).Secondary outcomes included deterioration of the osteonecrosis to a higher disease stage at 5 years compared to the preoperative period and identification of factors that were associated with survival.The Kaplan-Meier survival analysis was performed to evaluate the survivorship ofthe prosthesis,and the Fisher exact test was performed to test associations between various parameters with survival.RESULTS: No patient developed any serious intraoperative or postoperative complication including implant loosening or migration and donor site morbidity.During the 5-year follow up,1 patient died,7 patients had disease progression and 4 hips were converted to THA.The 5-year survival based on conversion to THA was 93.1% and the respective rate based on disease progression was 87.9%.Stage Ⅱ disease was associated with statistically significant better survival rates compared to stage Ⅲ disease(P = 0.04).The comparison between idiopathic and non-idiopathic osteonecrosis and between steroid-induced and non-steroid-induced osteonecrosis did not showed any statistically significant difference in survival rates.The clinical evaluation revealed statistically significantly improved Merle d'Aubigne scores at 12 mo postoperatively compared to the preoperative period(P < 0.001).The mean preoperative Merle d'Aubigne score was 13.0(SD: 1.8).The respective score at 12 mo improved to 17.0(SD: 2.0).The 12-mo mean score was retained at 5 years.CONCLUSION: The modified porous tantalum rod technique presented here showed encouraging outcomes.The survival rates based on conversion to THA are the lowest reported in the published literature. | Emilios E Pakos Panayiotis Megas Nikolaos K Paschos Spyridon A Syggelos Antonios Kouzelis Georgios Georgiadis Theodoros A Xenakis | 2015 | World Journal of Orthopedics2015,6,10: | 20 |
| 19 | 世界卫生组织(WHO)造血与淋巴组织肿瘤分类方案:临床顾问委员会会议报告显示文摘引言 :从 1995年开始 ,欧洲病理学工作者协会和血液病理学会一直致力于制定一个新的世界卫生组织 (WHO)血液恶性肿瘤分类方案 ,该分类方案包括淋巴系肿瘤、髓系肿瘤、组织细胞肿瘤和肥大细胞肿瘤。 材料与方法 :此项 WHO计划共组成十个病理学工作者委员会 ,负责确定病种和作出定义。另外还成立一个由国际血液学家和肿瘤学家组成的临床顾问委员会 (CAC)以保证该分类的临床实用性。 1997年 11月召开会议讨论了与该分类有关的临床问题。 结果 :WHO采纳了 1994年国际淋巴瘤研究组 (IL SG)报告的修订欧美淋巴系肿瘤分类 (REAL)方案作为淋巴系肿瘤的分类方案。该方案的分类方法遵循以下原则 :分类应是联合应用形态学、免疫表型、遗传特征及临床特征能够清楚界定的“真实存在”(“real”)病种的名录 ,上述各项特征的相对重要性因病种不同而异 ,不存在任何“金标准”。 WHO将 REAL分类原则延用于髓系肿瘤和组织细胞肿瘤 ,髓系肿瘤的分类包括联合应用细胞形态学和细胞遗传学异常能够界定的各个病种。围绕一系列临床问题召集的这次 CAC会议 ,就提交的大多数问题达成共识 ,这些问题及共识将详述于下。对于另外一些问题 ,CAC认为淋巴系肿瘤临床分组既无必要也不必需 ,患者的治疗取决于淋巴瘤的具体类型 ,如有? | N L Harris E S Jaffe J Diebold G Flandrin H K Muller-Hermelink J Vardiman T A Lister C D Bloomfield 张凤奎 郝玉书 | 2001 | 白血病.淋巴瘤2001,10,3: | 20 |
| 20 | 流体饱和多孔介质中热发展强迫对流的熵产分析显示文摘利用Darcy流动模型,同时考虑粘性耗散效应,分析研究了以两等温平板为边界的多孔介质中,热发展强迫对流的熵产.参数研究表明,组参数和Péclet数减小,而Brinkman数增大时,熵产增大.形象化的热线表示方法着重应用于Br<0的情况,在这种情况下,在顺流的某些位置上,存在热传递方向的改变,即从原来的壁面向外传热变为向壁面传热. | K·霍曼 A·伊济拉利 F·霍曼 吴承平(译) 张禄坤(校) | 2008 | 应用数学和力学2008,29,2: | 20 |