全文获取类型
收费全文 | 2924篇 |
免费 | 248篇 |
国内免费 | 358篇 |
出版年
2023年 | 80篇 |
2022年 | 61篇 |
2021年 | 97篇 |
2020年 | 121篇 |
2019年 | 196篇 |
2018年 | 168篇 |
2017年 | 152篇 |
2016年 | 129篇 |
2015年 | 82篇 |
2014年 | 172篇 |
2013年 | 241篇 |
2012年 | 117篇 |
2011年 | 166篇 |
2010年 | 118篇 |
2009年 | 147篇 |
2008年 | 134篇 |
2007年 | 152篇 |
2006年 | 122篇 |
2005年 | 96篇 |
2004年 | 117篇 |
2003年 | 105篇 |
2002年 | 104篇 |
2001年 | 57篇 |
2000年 | 52篇 |
1999年 | 60篇 |
1998年 | 40篇 |
1997年 | 34篇 |
1996年 | 38篇 |
1995年 | 32篇 |
1994年 | 35篇 |
1993年 | 32篇 |
1992年 | 34篇 |
1991年 | 25篇 |
1990年 | 19篇 |
1989年 | 20篇 |
1988年 | 18篇 |
1987年 | 17篇 |
1986年 | 12篇 |
1985年 | 18篇 |
1984年 | 20篇 |
1983年 | 17篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 8篇 |
1973年 | 8篇 |
1971年 | 4篇 |
排序方式: 共有3530条查询结果,搜索用时 15 毫秒
1.
《Bioorganic & medicinal chemistry》2020,28(11):115492
Effective chemotherapy for solid cancers is challenging due to a limitation in permeation that prevents anticancer drugs from reaching the center of the tumor, therefore unable to limit cancer cell growth. To circumvent this issue, we planned to apply the drugs directly at the center by first collapsing the outer structure. For this, we focused on cell–cell communication (CCC) between N-glycans and proteins at the tumor cell surface. Mature N-glycans establish CCC; however, CCC is hindered when numerous immature N-glycans are present at the cell surface. Inhibition of Golgi mannosidases (GMs) results in the transport of immature N-glycans to the cell surface. This can be employed to disrupt CCC. Here, we describe the molecular design and synthesis of an improved GM inhibitor with a non-sugar mimic scaffold that was screened from a compound library. The synthesized compounds were tested for enzyme inhibition ability and inhibition of spheroid formation using cell-based methods. Most of the compounds designed and synthesized exhibited GM inhibition at the cellular level. Of those, AR524 had higher inhibitory activity than a known GM inhibitor, kifunensine. Moreover, AR524 inhibited spheroid formation of human malignant cells at low concentration (10 µM), based on the disruption of CCC by GM inhibition. 相似文献
2.
《Bioorganic & medicinal chemistry》2020,28(24):115819
The exploitation of GLU988 and LYS903 residues in PARP1 as targets to design isoquinolinone (I & II) and naphthyridinone (III) analogues is described. Compounds of structure I have good biochemical and cellular potency but suffered from inferior PK. Constraining the linear propylene linker of structure I into a cyclopentene ring (II) offered improved PK parameters, while maintaining potency for PARP1. Finally, to avoid potential issues that may arise from the presence of an anilinic moiety, the nitrogen substituent on the isoquinolinone ring was incorporated as part of the bicyclic ring. This afforded a naphthyridinone scaffold, as shown in structure III. Further optimization of naphthyridinone series led to identification of a novel and highly potent PARP1 inhibitor 34, which was further characterized as preclinical candidate molecule. Compound 34 is orally bioavailable and displayed favorable pharmacokinetic (PK) properties. Compound 34 demonstrated remarkable antitumor efficacy both as a single-agent as well as in combination with chemotherapeutic agents in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. Additionally, compound 34 also potentiated the effect of agents such as temozolomide in breast cancer, pancreatic cancer and Ewing’s sarcoma models. 相似文献
3.
Three series of bitobic arylpiperazine-phenyl-hexahydropyrazinoquino- lines analogues were designed, synthesizedand evaluated as a novel class of selective ligands for the dopamine D3 receptor. Compounds 15a (Ki of 11.7 ± 1.8 and 373 nM at D3 and D2, respectively), 15c (Ki of 5.49 and 264 nM at D3 and D2, respectively), 15e (Ki of 14.9 and 325 nM at D3 and D2, respectively), 15i (Ki of 13.8 and 401 nM at D3 and D2, respectively) and 15l (Ki of 13.6 and 870 nM at D3 and D2, respectively) were found to demonstrate good binding affinity and selectivity, and especially compound 15c showeda similar binding affinity and selectivity compared with the contrast drug BP897. 相似文献
4.
为了从分子水平上评价中国大陆尼罗罗非鱼(Oreochromis niloticus)主要引进群体间遗传关系、遗传分化及基因流状况,研究利用12对多态性微卫星引物,以埃及土著群体为对照组,分析中国大陆尼罗罗非鱼9个代表性引进群体的遗传关系。结果显示:①群体间四种遗传距离[DA、DC、DSW和(δμ)2]同时表明,USA群体和EGY群体间的遗传距离最小[DA=0.2174,DC=0.4140,DSW=0.8769,(δμ)2=22.6904];DA和DC表明GD群体和XJF群体间遗传距离最大(DA=0.5851,DC=0.6789);DSW和(δμ)2表明USA群体与XJF群体间遗传距离最大[DSW=4.0907,(δμ)2=138.18]。② EGY群体和GD群体间遗传分化最小(FST=0.0326,RST=0.0337),XJF群体和LY群体间遗传分化最大(FST=0.2098,RST=0.2655)。所有成对群体间均存在显著的遗传分化(P < 0.05)。③群体间系统树显示,WY群体、GD群体、EGY群体和USA群体被聚为一类,BL群体、LY群体和EW群体被聚为一类,JNM群体和GLD群体被聚为一类,XJF群体位于独立的分支;贝叶斯聚类分析将10个群体划分为2类,XJF、BL、LY、EW群体被归入第一类,WY、GD、EGY、USA、GLD和JNM群体被归入第二类。分子方差分析和主成分分析支持了系统树和贝叶斯聚类分析的结果。④根据成对FST值和RST值估算的群体间历史基因流平均值分别为2.4427和2.1983。群体间近期基因流检测结果显示,各群体中发生第一代迁移的个体数在0-7个,占样本数的0-23.3%。总体而言,我国尼罗罗非鱼引进群体间遗传分化显著,群体间存在一定程度的历史基因流和近期基因流。研究结果为开展我国尼罗罗非鱼引进群体的种质资源保护和综合利用提供了科学依据。 相似文献
5.
6.
7.
The relationship between physicochemical factors and plankton abundance in the newly created Bui reservoir was studied during 2011 and 2012. The objective was to assess the influence of physicochemical factors on plankton abundance and provide data for monitoring the hydrobiology of the newly created Bui reservoir. Two sampling stations were selected on the Black Volta upstream (Bui) and downstream (Bamboi) of the dam, with samples taken pre‐ and postimpoundment during the study period. Canonical Correspondence Analysis (CCA) was used to trace temporal plankton community changes and to examine the relationships between species composition and physicochemical variables. The relative abundance of some phytoplankton species such as Anabaena sp., Planktothrix sp. and Scenedesmus sp. was directly correlated to nitrates. CCA indicated that physicochemical variables explained 41–64% of zooplankton and 8–12% of phytoplankton variation. Hence, there were correlations between environmental variables and the structure of plankton assemblages. This feature should therefore be used for bio‐monitoring of environmental variables of the river by the Bui Power Authority to ensure protection of the aquatic biota downstream of the Bui dam. 相似文献
8.
F. -W. Bentrup 《European biophysics journal : EBJ》1980,6(3):175-189
This review treats some examples of electrogenic transport across the outer plasmamembrane (plasmalemma) of plant cells. The selection includes primary active uniport by membrane ATPases (e.g., the proton pump), secondary active transport of hexoses by proton-dependent cotransport, and passive uniport of amines. Primacy is given to the presentation of electrophysiological data and to the discussion of voltage-dependence of the transport mechanisms.Lecture from the Annual Meeting of the Deutsche Gesellschaft für Biophysik at Konstanz 相似文献
9.
Stanislav Lhota Veronika Roubov Vendula Gregorov Martina Kone
n 《American journal of primatology》2019,81(9)
Grooming in primates is often considered a “currency” that can be exchanged for other “services” or “commodities” such as reciprocal grooming, coalitionary support, infant handling, tolerance around food sources, active food sharing, or mating opportunities. Previous studies on primate grooming‐for‐sex exchange viewed the males as the demanding class, with the females as suppliers of mating opportunities. In this study, we examine the broader context of grooming‐for‐mating exchange in Barbary macaques in Gibraltar. Our data show that Barbary macaque males groom females with whom they are mating more frequently and for longer periods than other females, and the relationship between grooming and mating remains significant in both sexual and nonsexual contexts. In addition, females groomed males with whom they were mating more frequently and for longer periods than other males. In both sexes, grooming was observed to be far more frequent and to occur for longer durations in sexual compared to nonsexual contexts. We did not find any difference in grooming behavior between presexual and postsexual contexts. Our data suggest that there is no simple model to describe Barbary macaque grooming patterns in sexual contexts. Although our results are partly consistent with male use of grooming as payment for mating, broadly assessed grooming‐mating patterns cannot be solely explained by a male‐driven grooming‐for‐mating exchange. 相似文献
10.
Cross-scale vegetation patterns of Flooding Pampa grasslands 总被引:11,自引:0,他引:11