全文获取类型
收费全文 | 1016篇 |
免费 | 59篇 |
国内免费 | 1篇 |
专业分类
1076篇 |
出版年
2023年 | 4篇 |
2022年 | 13篇 |
2021年 | 28篇 |
2020年 | 18篇 |
2019年 | 23篇 |
2018年 | 28篇 |
2017年 | 22篇 |
2016年 | 24篇 |
2015年 | 58篇 |
2014年 | 52篇 |
2013年 | 88篇 |
2012年 | 122篇 |
2011年 | 102篇 |
2010年 | 53篇 |
2009年 | 45篇 |
2008年 | 46篇 |
2007年 | 51篇 |
2006年 | 36篇 |
2005年 | 41篇 |
2004年 | 24篇 |
2003年 | 13篇 |
2002年 | 25篇 |
2001年 | 13篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 11篇 |
1978年 | 3篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 3篇 |
1970年 | 4篇 |
1964年 | 1篇 |
排序方式: 共有1076条查询结果,搜索用时 15 毫秒
31.
Jalan-Sakrikar N Bartlett RK Baucum AJ Colbran RJ 《The Journal of biological chemistry》2012,287(19):15275-15283
Protein-protein interactions are thought to modulate the efficiency and specificity of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) signaling in specific subcellular compartments. Here we show that the F-actin-binding protein α-actinin targets CaMKIIα to F-actin in cells by binding to the CaMKII regulatory domain, mimicking CaM. The interaction with α-actinin is blocked by CaMKII autophosphorylation at Thr-306, but not by autophosphorylation at Thr-305, whereas autophosphorylation at either site blocks Ca(2+)/CaM binding. The binding of α-actinin to CaMKII is Ca(2+)-independent and activates the phosphorylation of a subset of substrates in vitro. In intact cells, α-actinin selectively stabilizes CaMKII association with GluN2B-containing glutamate receptors and enhances phosphorylation of Ser-1303 in GluN2B, but inhibits CaMKII phosphorylation of Ser-831 in glutamate receptor GluA1 subunits by competing for activation by Ca(2+)/CaM. These data show that Ca(2+)-independent binding of α-actinin to CaMKII differentially modulates the phosphorylation of physiological targets that play key roles in long-term synaptic plasticity. 相似文献
32.
33.
Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems, a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3?4 μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210±30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1. 相似文献
34.
Vivek Kumar Mukesh M. Mudgal Nidhi Rani Amrita Jha Manu Jaggi Anu T. Singh 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):763-770
A new series of functionalized amino acid derivatives N-substituted 1-N-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyl-5-oxazolidine carboxamide (1-17) and 1-N-substituted-3-amino-2-hydroxy-3-phenylpropane-1-carboxamide (18-34) were synthesized and evaluated for their in vitro cytotoxicity against human cancer cell lines. Compound 6 has shown interesting cytotoxicity (IC50 = 5.67 μm) in ovarian cancer, while compound 10 exhibited promising cytotoxicity in ovarian (IC50 = 6.1 μm) and oral (IC50 = 4.17 μm) cancers. These compounds could be of use in designing new anti-cancer agents. 相似文献
35.
Heinen CD Cyr JL Cook C Punja N Sakato M Forties RA Lopez JM Hingorani MM Fishel R 《The Journal of biological chemistry》2011,286(46):40287-40295
The mechanics of hMSH2-hMSH6 ATP binding and hydrolysis are critical to several proposed mechanisms for mismatch repair (MMR), which in turn rely on the detailed coordination of ATP processing between the individual hMSH2 and hMSH6 subunits. Here we show that hMSH2-hMSH6 is strictly controlled by hMSH2 and magnesium in a complex with ADP (hMSH2(magnesium-ADP)-hMSH6). Destabilization of magnesium results in ADP release from hMSH2 that allows high affinity ATP binding by hMSH6, which then enhances ATP binding by hMSH2. Both subunits must be ATP-bound to efficiently form a stable hMSH2-hMSH6 hydrolysis-independent sliding clamp required for MMR. In the presence of magnesium, the ATP-bound sliding clamps remain on the DNA for ~8 min. These results suggest a precise stepwise kinetic mechanism for hMSH2-hMSH6 functions that appears to mimic G protein switches, severely constrains models for MMR, and may partially explain the MSH2 allele frequency in Lynch syndrome or hereditary nonpolyposis colorectal cancer. 相似文献
36.
Om Parkash Mittal 《Genetica》1967,38(1):516-520
Gnaphosa kailana Tikader andScotophaeus blackwallii (Thorell) are characterized by twenty-two (20+X1X2) and twenty-four (22+X1X2) acrocentric chromosomes in their diploid set respectively. In case ofG. kailana the sex-chromosomes are slightly unequal while inS. blackwallii the size difference is well marked between the two. The sex-chromosomes in both species form an accessory plate at the equator of the spindle during metaphase-I and show a precocious anaphase-I movement. 相似文献
37.
Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury 总被引:1,自引:0,他引:1
Shervington A Cruickshanks N Wright H Atkinson-Dell R Lea R Roberts G Shervington L 《Molecular and cellular biochemistry》2006,283(1-2):1-9
The continuous advancements in cancer research have contributed to the overwhelming evidence of the presence of telomerase
in primary and secondary tumours together with hsp90 and c-Myc. This review will discuss the important role of telomerase together with hsp90 and c-Myc within the initiation and progression of gliomas. Also it will review the differential expression of these genes in the different
grades of gliomas and the possibility of new treatments targeting these specific genes. 相似文献
38.
39.
Several derivatives of hadacidin have been developed and evaluated for activity against adenylosuccinate synthetase. 相似文献
40.
Khanna S Venojarvi M Roy S Sharma N Trikha P Bagchi D Bagchi M Sen CK 《Free radical biology & medicine》2002,33(8):1089-1096