全文获取类型
收费全文 | 4613篇 |
免费 | 465篇 |
国内免费 | 301篇 |
出版年
2023年 | 111篇 |
2022年 | 74篇 |
2021年 | 131篇 |
2020年 | 193篇 |
2019年 | 274篇 |
2018年 | 224篇 |
2017年 | 195篇 |
2016年 | 185篇 |
2015年 | 158篇 |
2014年 | 275篇 |
2013年 | 367篇 |
2012年 | 160篇 |
2011年 | 230篇 |
2010年 | 186篇 |
2009年 | 210篇 |
2008年 | 249篇 |
2007年 | 231篇 |
2006年 | 243篇 |
2005年 | 201篇 |
2004年 | 193篇 |
2003年 | 183篇 |
2002年 | 145篇 |
2001年 | 105篇 |
2000年 | 81篇 |
1999年 | 82篇 |
1998年 | 86篇 |
1997年 | 66篇 |
1996年 | 61篇 |
1995年 | 58篇 |
1994年 | 55篇 |
1993年 | 39篇 |
1992年 | 47篇 |
1991年 | 28篇 |
1990年 | 16篇 |
1989年 | 22篇 |
1988年 | 19篇 |
1987年 | 24篇 |
1986年 | 24篇 |
1985年 | 21篇 |
1984年 | 11篇 |
1983年 | 10篇 |
1982年 | 18篇 |
1981年 | 7篇 |
1980年 | 17篇 |
1979年 | 8篇 |
1978年 | 12篇 |
1977年 | 9篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1971年 | 5篇 |
排序方式: 共有5379条查询结果,搜索用时 46 毫秒
971.
The use of existing drugs for new therapeutic applications, commonly referred to as drug repositioning, is a way for fast and cost-efficient drug discovery. Drug repositioning in oncology is commonly initiated by in vitro experimental evidence that a drug exhibits anticancer cytotoxicity. Any independent verification that the observed effects in vitro may be valid in a clinical setting, and that the drug could potentially affect patient survival in vivo is of paramount importance. Despite considerable recent efforts in computational drug repositioning, none of the studies have considered patient survival information in modelling the potential of existing/new drugs in the management of cancer. Therefore, we have developed DRUGSURV; this is the first computational tool to estimate the potential effects of a drug using patient survival information derived from clinical cancer expression data sets. DRUGSURV provides statistical evidence that a drug can affect survival outcome in particular clinical conditions to justify further investigation of the drug anticancer potential and to guide clinical trial design. DRUGSURV covers both approved drugs (∼1700) as well as experimental drugs (∼5000) and is freely available at http://www.bioprofiling.de/drugsurv. 相似文献
972.
Optimal surveillance strategy for invasive species management when surveys stop after detection
下载免费PDF全文
![点击此处可从《Ecology and evolution》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Gurutzeta Guillera‐Arroita Cindy E. Hauser Michael A. McCarthy 《Ecology and evolution》2014,4(10):1751-1760
Invasive species are a cause for concern in natural and economic systems and require both monitoring and management. There is a trade‐off between the amount of resources spent on surveying for the species and conducting early management of occupied sites, and the resources that are ultimately spent in delayed management at sites where the species was present but undetected. Previous work addressed this optimal resource allocation problem assuming that surveys continue despite detection until the initially planned survey effort is consumed. However, a more realistic scenario is often that surveys stop after detection (i.e., follow a “removal” sampling design) and then management begins. Such an approach will indicate a different optimal survey design and can be expected to be more efficient. We analyze this case and compare the expected efficiency of invasive species management programs under both survey methods. We also evaluate the impact of mis‐specifying the type of sampling approach during the program design phase. We derive analytical expressions that optimize resource allocation between monitoring and management in surveillance programs when surveys stop after detection. We do this under a scenario of unconstrained resources and scenarios where survey budget is constrained. The efficiency of surveillance programs is greater if a “removal survey” design is used, with larger gains obtained when savings from early detection are high, occupancy is high, and survey costs are not much lower than early management costs at a site. Designing a surveillance program disregarding that surveys stop after detection can result in an efficiency loss. Our results help guide the design of future surveillance programs for invasive species. Addressing program design within a decision‐theoretic framework can lead to a better use of available resources. We show how species prevalence, its detectability, and the benefits derived from early detection can be considered. 相似文献
973.
Anion exchange (AEX) is a common downstream purification operation for biotechnology products manufactured in cell culture such as therapeutic monoclonal antibodies (mAbs) and Fc‐fusion proteins. We present a head‐to‐head comparison of the viral clearance efficiency of AEX adsorbers and column chromatography using the same process fluids and comparable run conditions. We also present overall trends from the CDER viral clearance database. In our comparison of multiple brands of resins and adsorbers, clearance of three model viruses (PPV, X‐MuLV, and PR772) was largely comparable, with some exceptions which may reflect run conditions that had not been optimized on a resin/membrane specific basis. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:124–131, 2014 相似文献
974.
重大工程建设中生态安全格局构建基本原则和方法 总被引:9,自引:0,他引:9
随着人类活动的日益加强,生态安全成为全球关注的话题.生态安全的状态受到人类干扰活动的影响,而区域生态安全演变也会影响人类活动的功效.20世纪90年代以来,我国先后开展了长江三峡大坝、青藏铁路、西气东输、西电东送、南水北调等重大工程项目的建设.这些重大工程建设对区域生态安全的影响,以及区域生态系统演变对工程安全运行的影响成为我国政府关注的重要课题.如何在强度干扰下开展生态恢复与区域生态安全格局的构建,不仅关系到区域生态环境的保护,也关系到各项重大工程的顺利运行.本文系统分析了工程建设的类型、特征及其对区域生态环境的影响,在此基础上,提出了重大工程建设中生态恢复与安全格局构建的基本原则和方法.认为在工程建设中构建生态安全格局需要从6个方面着手:区域生态环境现状分析与评价、工程建设生态干扰与风险评价、生态安全格局预案构建、区域生态环境效应情景分析、区域生态恢复与安全格局再优化和生态系统管理方案的建立.讨论了我国重大工程建设中生态安全格局构建面临的突出问题. 相似文献
975.
976.
蜜环菌诱导子对丹参冠瘿组织积累丹参酮的影响 总被引:2,自引:0,他引:2
以 6 7_V液体培养基为基本培养基 ,利用计算机软件“均匀设计、回归分析及优化系统” ,研究了蜜环菌(ArmillariamelleaKarst)诱导子浓度、诱导子的加入时间与处理的收获时间对丹参 (SalviamiltiorrhizaBunge)冠瘿组织积累丹参酮的影响。结果表明 ,蜜环菌诱导子浓度为 119mL/L、第 0天加入诱导子、第 2 9天收获培养物与培养液时可获得最高的丹参酮生产量 (147mg/L ,P <0 .0 5 ) ,蜜环菌诱导子浓度为 113mL/L、第 0天加入诱导子、第 2 6天收获培养液时可获得最高的丹参酮生产量 (6 2mg/L ,P <0 .0 5 ) ,蜜环菌诱导子浓度为 87mL/L、第 0天加入诱导子、第2 8天收获培养物时可获得最高的丹参酮生产量 (94mg/L ,P <0 .0 5 )。结果证实 ,计算机软件“均匀设计、回归分析及优化系统”对于观察值受多因素影响的研究非常有效和方便。 相似文献
977.
Erkang Fan Ethan A Merritt Christophe LMJ Verlinde Wim GJ Hol 《Current opinion in structural biology》2000,10(6)
High-resolution crystal structures of AB5 toxins in their native form or in complex with a variety of ligands have led to the structure-based design and discovery of inhibitors targeting different areas of the toxins. The most significant progress is the development of highly potent multivalent ligands that block binding of the toxins to their receptors. 相似文献
978.
催化抗体研究新进展 总被引:3,自引:0,他引:3
罗贵民 《生物化学与生物物理进展》2000,27(4):354-359
催化抗体也叫抗体酶,是具有催化活性的免疫球蛋白.由于它兼具抗体的高度选择性和酶的高效催化性,因而催化抗体制备技术的开发预示着可以人为生产适应各种用途的,特别是自然界不存在的高效催化剂,对生物学、化学和医学等多种学科有重要的理论意义和实用价值.综述了催化抗体研究的最新进展,讨论了该领域目前存在的问题,提出了解决这些问题的可能办法. 相似文献
979.
红豆杉细胞悬浮培养中不同添加物对细胞生长和紫杉醇合成的影响 总被引:6,自引:1,他引:5
采用正交实验检测红豆杉(Taxus chinensis(Pilger)Rehd.)细胞悬浮培养中水杨酸、D-果糖、甘露醇和硫酸镧对细胞生长和紫杉醇(taxol)积累的影响。添加10g/LD-果糖,可使细胞的鲜重和干重明显增加;添加60g/L甘露醇使细胞的鲜重和干重明显减少;1mg/L水杨酸仅使细胞鲜重增加,对干重影响不明显;硫酸镧对细胞生长无明显影响。单独添加这4种物质,紫杉醇含量均下降,同时添加 相似文献
980.
Florence L. Stahura Ling Xue Jeffrey W. Godden Jürgen Bajorath 《Journal of molecular modeling》2000,6(7-8):550-562
A new approach to the design of compound libraries, named MetaFocus (Metabolite-Focused library), is presented that exploits information encoded in natural molecules and combines naturally occurring and synthetic compounds. An important goal of the MF approach is the identification of synthetic compounds that mimic properties of natural molecules that are difficult to obtain in sufficient quantities or to synthesize. Compounds in MetaFocus (MF) arrays are focused on natural molecules with attractive therapeutic effects. Similarity search and diversity design techniques are employed to generate compound arrays that start from a selected natural molecule, add similar molecules, either from natural or synthetic sources, and diversify scaffolds derived from these molecules. Since the identification of similar molecules from natural and synthetic sources plays a significant role in our library design efforts, the performance of fingerprint-type search tools was systematically assessed in a newly assembled test database consisting of 16 biological activity classes. MF arrays are organized as an easily expandable and searchable data structure and serve as a knowledge base for drug discovery applications. Here we introduce the design principles and organization of MF arrays and present example applications. 相似文献