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排序方式: 共有308条查询结果,搜索用时 11 毫秒
301.
Magdalena C Liebl Jutta Moehlenbrink Huong Becker Günter Raddatz Suhaib
K Abdeen Rami I Aqeilan Frank Lyko Thomas G Hofmann 《Nucleic acids research》2021,49(5):2759
The DNA damage-responsive tumor suppressors p53 and HIPK2 are well established regulators of cell fate decision-making and regulate the cellular sensitivity to DNA-damaging drugs. Here, we identify Deleted in Azoospermia-associated protein 2 (DAZAP2), a small adaptor protein, as a novel regulator of HIPK2 and specifier of the DNA damage-induced p53 response. Knock-down or genetic deletion of DAZAP2 strongly potentiates cancer cell chemosensitivity both in cells and in vivo using a mouse tumour xenograft model. In unstressed cells, DAZAP2 stimulates HIPK2 polyubiquitination and degradation through interplay with the ubiquitin ligase SIAH1. Upon DNA damage, HIPK2 site-specifically phosphorylates DAZAP2, which terminates its HIPK2-degrading function and triggers its re-localization to the cell nucleus. Interestingly, nuclear DAZAP2 interacts with p53 and specifies target gene expression through modulating a defined subset of p53 target genes. Furthermore, our results suggest that DAZAP2 co-occupies p53 response elements to specify target gene expression. Collectively, our findings propose DAZAP2 as novel regulator of the DNA damage-induced p53 response that controls cancer cell chemosensitivity. 相似文献
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Stephen M. Coutts Detlev Riesner Roland Römer Cad R. Rabl Guenter Maass 《Biophysical chemistry》1975,3(4):275-289
The kinetics of the melting transitions of tRNAphe (yeast) were followed by the fluorescence of the Y-base and of formycin substituted for the 3'-terminal adenine. As judged from differential UV absorbance melting cutves the formycin label had virtually no influence on the conformation of the tRNA. A temperature jump apparatus was modified to allow the simultaneous observation of transmission and fluorescence intensities by two independent optical channels. The design of a temperature jump cell with an all quartz center piece is given. The cell is resistant to temperatures up to 90°C; it provides high optical sensitivity, low stray light intensity and the possibility of measuring fluorescence polarization. The T-jump experiments allowed to discriminate between fast unspecific fluorescence quenching (τ <5 μsec) and slow co-operative conformational changes. In the central part of the temperature range of UV-melung (midpoint temperature 30°C in 0.01 M Na+ and 39°C in 0.03 M Na+, pH 6.8) two resolvable relaxation processes were observed. The coirssponding relaxation times were 20 msec and 800 msec at 30°C in 0.01 M Na+, and 4 msec and 120 msec at 39°C in 0.03 M Na+. The Y-base fluorescence shows both of the relaxation effects, which almost cancel in equilibrium fluorescence melting, because their amplitudes have opposite signs. From this finding the existence of some residual tertiary structure is inferred which persists after the unfolding of the main part of tertiary structure durirg early melting (midpoint temperature 24°C in 0.03 M Na+). In the fluorescence sigXXX of the formycin also the two relaxation effects appear. Both of them are connected with a decrease of the fluorescence intensity. From the results a coupled opening of the anticodon and acceptor branches is concluded.Enzymes: phenylalanyl-tRNA synthetase, PRS (EC 6.1.1.-20); ATP (CTP) tRNA nucleotidyl transferase, NT (EC 2.7.7.-20); alkaline phosphatase (EC 3-1-3.1). 相似文献
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Blood affinity for oxygen in hemorrhagic and endotoxic shock 总被引:1,自引:0,他引:1
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