全文获取类型
收费全文 | 21249篇 |
免费 | 1501篇 |
国内免费 | 11篇 |
出版年
2023年 | 54篇 |
2022年 | 138篇 |
2021年 | 415篇 |
2020年 | 247篇 |
2019年 | 310篇 |
2018年 | 531篇 |
2017年 | 394篇 |
2016年 | 684篇 |
2015年 | 1126篇 |
2014年 | 1228篇 |
2013年 | 1396篇 |
2012年 | 1827篇 |
2011年 | 1710篇 |
2010年 | 1100篇 |
2009年 | 916篇 |
2008年 | 1348篇 |
2007年 | 1186篇 |
2006年 | 1053篇 |
2005年 | 971篇 |
2004年 | 959篇 |
2003年 | 777篇 |
2002年 | 785篇 |
2001年 | 627篇 |
2000年 | 632篇 |
1999年 | 424篇 |
1998年 | 172篇 |
1997年 | 132篇 |
1996年 | 119篇 |
1995年 | 87篇 |
1994年 | 82篇 |
1993年 | 69篇 |
1992年 | 157篇 |
1991年 | 125篇 |
1990年 | 88篇 |
1989年 | 104篇 |
1988年 | 70篇 |
1987年 | 66篇 |
1986年 | 69篇 |
1985年 | 54篇 |
1984年 | 47篇 |
1983年 | 37篇 |
1982年 | 28篇 |
1981年 | 24篇 |
1978年 | 28篇 |
1977年 | 23篇 |
1976年 | 32篇 |
1975年 | 30篇 |
1973年 | 33篇 |
1971年 | 23篇 |
1969年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
Stearns BA Anker N Arruda JM Campbell BT Chen C Cramer M Hu T Jiang X Park K Ren KK Sablad M Santini A Schaffhauser H Urban MO Munoz B 《Bioorganic & medicinal chemistry letters》2004,14(5):1295-1298
A novel class of 6-aryl-6H-pyrrolo[3,4-d]pyridazine ligands for the alpha2delta subunit of voltage-gated calcium channels has been described. Substitutions in the aryl ring of the molecule were generally not tolerated, and resulted in diminished binding to the alpha2delta subunit. Modifications to the pyridazine ring revealed numerous permissive substitutions, and detailed SAR studies were carried out in this portion of the molecule. Replacement of the pyridazine ring methyl group with an aminomethyl functionality provided greatly improved potency over the initial lead. The initial lead compound displayed good rat pharmacokinetic properties, and was shown to be efficacious in the Chung model for neuropathic pain in rats. 相似文献
952.
Lee WS Lee DW Baek YI An S An SJ Cho KH Choi YK Kim HC Park HY Bae KH Jeong TS 《Bioorganic & medicinal chemistry letters》2004,14(12):3109-3112
The sesquineolignan, saucerneol B (1), and dineolignans, manassantin A (2), and manassantin B (3), were isolated from the methanol extracts of Saururus chinensis root and elucidated by their spectroscopic data analysis. Compounds 1-3 inhibited hACAT-1 and hACAT-2 with IC(50) values of 43.0 and 124.0 microM for 1, of 39.0 and 8.0 microM for 2, of 82.0 microM and only 32% inhibition at 1mM for 3, respectively. The EtOAc-soluble fraction, which contained compounds 1-3, of methanol extracts of S. chinensis exhibited strong cholesterol-lowering effect in high cholesterol-fed mice. 相似文献
953.
Park HG Choi JY Choi SH Park MK Lee J Suh YG Cho H Oh U Kim HD Joo YH Kim SY Park YH Jeong YS Choi JK Kim JK Jew SS 《Bioorganic & medicinal chemistry letters》2004,14(7):1693-1696
A series of N-4-methansulfonamidobenzyl-N'-2-substituted-4-tert-butylbenzyl thioureas were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor in rat DRG neurons. Their structure-activity relationship reveals that there is a space for another hydrophobic binding interaction around 2-position in 4-tert-butylbenzyl region. Among the prepared derivatives, 6n show the highest antagonistic activity against the vanilloid receptor (IC(50)=15 nM). 相似文献
954.
Synthesis and biological activity of new quinoxaline antibiotics of echinomycin analogues 总被引:5,自引:0,他引:5
Novel quinoxaline antibiotics having the methylenedithioether bridge as an analogue of echinomycin have been synthesized by insertion of methylene moiety between -S-S- bond. The compound 1a shows remarkable cytotoxicities against human tumor various cell lines, and is active VRE (vancomycin-resistant enterococci) within MIC range 0.5-8 microg/mL. According to the eukaryotic or prokaryotic data, 1a might be a first analogue to replace echinomycin. 相似文献
955.
Induction of G2/M cell cycle arrest and apoptosis by a benz[f]indole-4,9-dione analog in cultured human lung (A549) cancer cells 总被引:1,自引:0,他引:1
Lee EJ Lee HJ Park HJ Min HY Suh ME Chung HJ Lee SK 《Bioorganic & medicinal chemistry letters》2004,14(20):5175-5178
A synthetic benz[f]indole-4,9-dione analog, 2-amino-3-ethoxycarbonyl-N-methylbenz[f]indole-4,9-dione (SME-6), showed a potent growth inhibition of a panel of human cancer cell lines. The mechanism of action study revealed that the growth inhibitory effect of SME-6 was highly related to the induction of G2/M cell cycle arrest and apoptosis in human lung cancer cells (A549). These data may provide new information for understanding the mechanisms by benz[f]indole-4,9-diones-mediated antitumor activity. 相似文献
956.
Homolasonolide A and 10-desmethyllasonolide A are biologically less active than lasonolide A. The ethyl ester analogue of lasonolide A exhibited higher activity than the parent compound in some biological test. 相似文献
957.
Park HG Choi JY Choi SH Park MK Lee J Suh YG Cho H Oh U Lee J Kang SU Lee J Kim HD Park YH Su Jeong Y Kyu Choi J Jew SS 《Bioorganic & medicinal chemistry letters》2004,14(3):787-791
A series of N-4-substituted-benzyl-N'-tert-butylbenzyl thioureas were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor in rat DRG neurons. Their structure-activity relationship reveals that not only the two oxygens and amide hydrogen of sulfonamido group, but also the optimal size of methyl in methanesulfonamido group play an integral role for the antagonistic activity on vanilloid receptor. 相似文献
958.
Oh M Im I Lee YJ Kim YH Yoon JH Park HG Higashiyama S Kim YC Park WJ 《Bioorganic & medicinal chemistry letters》2004,14(24):6071-6074
We describe a series of potent and selective inhibitors of ADAM12 that were discovered using computational screening of a focused virtual library. The initial structure-based virtual screening selected 64 compounds from a 3D database of 67,062 molecules. Being evaluated by a cell-based ADAM12 activity assay, compounds 5, 11, 14, 16 were further identified as the potent and selective inhibitors of ADAM12 with low nanomolar IC50 values. The mechanism underlying the potency and selectivity of a representative compound, 5, was investigated through molecular docking studies. 相似文献
959.
960.
Structural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway 总被引:6,自引:0,他引:6
CAD/DFF40 is responsible for the degradation of chromosomal DNA into nucleosomal fragments and subsequent chromatin condensation during apoptosis. It exists as an inactive complex with its inhibitor ICAD/DFF45 in proliferating cells but becomes activated upon cleavage of ICAD/DFF45 into three domains by caspases in dying cells. The molecular mechanism underlying the control and activation of CAD/DFF40 was unknown. Here, the crystal structure of activated CAD/DFF40 reveals that it is a pair of molecular scissors with a deep active-site crevice that appears ideal for distinguishing internucleosomal DNA from nucleosomal DNA. Ensuing studies show that ICAD/DFF45 sequesters the nonfunctional CAD/DFF40 monomer and is also able to disassemble the functional CAD/DFF40 dimer. This capacity requires the involvement of the middle domain of ICAD/DFF45, which by itself cannot remain bound to CAD/DFF40 due to low binding affinity for the enzyme. Thus, the consequence of the caspase-cleavage of ICAD/DFF45 is a self-assembly of CAD/DFF40 into the active dimer. 相似文献