全文获取类型
收费全文 | 955篇 |
免费 | 196篇 |
国内免费 | 21篇 |
专业分类
化学 | 645篇 |
力学 | 14篇 |
综合类 | 32篇 |
数学 | 377篇 |
物理学 | 104篇 |
出版年
2024年 | 1篇 |
2023年 | 15篇 |
2022年 | 33篇 |
2021年 | 112篇 |
2020年 | 93篇 |
2019年 | 63篇 |
2018年 | 59篇 |
2017年 | 60篇 |
2016年 | 74篇 |
2015年 | 68篇 |
2014年 | 74篇 |
2013年 | 82篇 |
2012年 | 48篇 |
2011年 | 46篇 |
2010年 | 35篇 |
2009年 | 40篇 |
2008年 | 27篇 |
2007年 | 36篇 |
2006年 | 30篇 |
2005年 | 29篇 |
2004年 | 31篇 |
2003年 | 12篇 |
2002年 | 16篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 13篇 |
1998年 | 8篇 |
1997年 | 7篇 |
1996年 | 2篇 |
1995年 | 11篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有1172条查询结果,搜索用时 328 毫秒
1.
《Arabian Journal of Chemistry》2022,15(1):103492
Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression. A variety of chemical classes have been explored for targeting individual MMP isoforms. In the present study, we further developed our isatin based scaffold BB0223107 capable of binding to and inactivating MMP-2 in a zinc-independent manner (Agamennone et al., 2016). Forty four new compounds were synthesized based on the modified BB0223107. All compounds were tested in enzyme inhibition assays against MMP-2, ?8 and ?13. SAR studies demonstrated that 5-het(aryl)-3-aminoindolin-2-ones (37–39) were active toward MMP-2 and MMP-13. The most potent compounds 33 and 37 displayed an IC50 of 3 µM against MMP-13 and showed a negligible activity toward MMP-8; almost all new compounds were inactive toward MMP-8. Replacement of the isatin ring with a biaryl system (compound 33) did not decrease the potency against MMP-13 but reduced the selectivity. Structure-based computational studies were carried out to rationalize the inhibitory activity data. The analysis of binding geometries confirmed that all fragments occupied the S1′ site in the three enzymes while no ligand was able to bind the catalytic zinc ion. To the best of our knowledge, this is the first example of 3-aminoindolin-2-one-based MMP inhibitors that, based on the computer modeling study, do not coordinate the zinc ion. Thus, the het(aryl)-3-aminoindolin-2-one derivatives emerge as a drug-like and promising chemotype that, along with the hetaryl variations, represents an alternative and thrifty tool for chemical space exploration aimed at MMP inhibitor design. 相似文献
2.
Rongzhen Wu Hongyu Chen Dr. Ninghui Chang Yuzhi Xu Prof. Dr. Jiao Jiao Prof. Dr. Hailong Zhang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(6):1166-1195
Bryostatins are a class of naturally occurring macrocyclic lactones with a unique fast developing portfolio of clinical applications, including treatment of AIDS, Alzheimer's disease, and cancer. This comprehensive account summarizes the recent progress (2014–present) in the development of bryostatins, including their total synthesis and biomedical applications. An emphasis is placed on the discussion of bryostatin 1 , the most-studied analogue to date. This review highlights the synthetic and biological challenges of bryostatins and provides an outlook on their future development. 相似文献
3.
本文是文[1-7]的继续,研究变权综合问题,从确定变权的经验公式入手引出了变权原理,给出了变权的公理化定义,讨论了与之有关的均衡函数及其梯度向量。 相似文献
4.
关联规则是数据挖掘中的重要研究内容之一,对在事务数据库不变,只对最小支持度和最小可信度进行改变的情况下,针对关联规则的维护问题,设计了一个增量式更新的改进算法AIUA。 相似文献
5.
6.
基于粗糙集理论的知识约简及应用实例 总被引:5,自引:0,他引:5
在保持分类能力不变的前提下 ,通过利用粗糙集理论中的知识约简方法 ,在保护知识库分类不变的条件下 ,删除其中不相关或不重要的知识 ,从而导出问题的决策 .利用基于决策表的粗糙集模型算法 ,实例分析如何数字化表示决策表 ,并对其进行属性约简和属性值的约简 ,从而提取决策规则 . 相似文献
7.
Bernhard Heinemann 《Mathematical Logic Quarterly》1997,43(2):203-215
Based on a modification of Moss' and Parikh's topological modal language [8], we study a generalization of a weakly expressive fragment of a certain propositional modal logic of time. We define a bimodal logic comprising operators for knowledge and nexttime. These operators are interpreted in binary computation structures. We present an axiomatization of the set T of theorems valid for this class of semantical domains and prove – as the main result of this paper – its completeness. Moreover, the question of decidability of T is treated. 相似文献
8.
9.
10.