全文获取类型
收费全文 | 278篇 |
免费 | 16篇 |
出版年
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 13篇 |
2013年 | 8篇 |
2012年 | 10篇 |
2011年 | 14篇 |
2010年 | 3篇 |
2009年 | 5篇 |
2008年 | 16篇 |
2007年 | 11篇 |
2006年 | 13篇 |
2005年 | 14篇 |
2004年 | 17篇 |
2003年 | 12篇 |
2002年 | 13篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 11篇 |
1990年 | 5篇 |
1989年 | 10篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有294条查询结果,搜索用时 15 毫秒
71.
Substrates for mitotic proteolysis such as cyclin B have a 9 residue destruction motif, the destruction box (D-box). To identify the receptor that specifically binds the D-box, we used affinity chromatography with immobilized D-box matrices. We find that the APC/C from Xenopus egg extracts binds to the D-box of cyclin B, whereas Fizzy (Cdc20) does not. Mutations in the D-box abolished this interaction. We show that this binding is regulated in the cell cycle, such that the APC/C from egg extracts in interphase does not bind to the D-box matrix. Our results suggest that the APC/C forms a stable interaction with the D-box of its substrates in a cell cycle-dependent manner. 相似文献
72.
Wakasugi K Slike BM Hood J Ewalt KL Cheresh DA Schimmel P 《The Journal of biological chemistry》2002,277(23):20124-20126
The first step of protein synthesis is catalyzed by aminoacyl-tRNA synthetases. In addition, certain mammalian tRNA synthetases link protein synthesis to cytokine signaling pathways. In particular, human tyrosyl-tRNA synthetase (TyrRS) can be split by proteolysis into two fragments having distinct cytokine activities. One of the TyrRS fragments (mini TyrRS) contains features identical to those in CXC chemokines (like interleukin-8) that also act as angiogenic factors. Here mini TyrRS (but not full-length TyrRS) is shown to stimulate chemotaxis of endothelial cells in vitro and stimulate angiogenesis in each of two in vivo animal models. The angiogenic activity of mini TyrRS can be opposed by anti-angiogenic chemokines like IP-10. Thus, a biological fragment of human tyrosyl-tRNA synthetase links protein synthesis to regulation of angiogenesis. 相似文献
73.
O-Wang J Kajiwara K Kawamura K Kimura M Miyagishima H Koseki H Tagawa M 《Biochemical and biophysical research communications》2002,293(3):1132-1137
The REV3 gene of budding yeast encodes the catalytic subunit of DNA polymerase zeta that carries out translesion DNA synthesis. While REV3-null yeast mutants are viable and exhibit normal growth, Rev3-deficient mice die around midgestation of embryogenesis, which is accompanied by massive apoptosis of cells within the embryo proper. We have investigated whether REV3 is required for the survival of mouse cells and whether the embryonic lethality caused by REV3 deficiency can be rescued by introduction of a Rev3 transgene or by inactivation of p53, the cellular gatekeeper that regulates DNA damage-induced apoptosis. We show that Rev3(-/-) blastocysts were unable to survive and grow in culture but expression of a Rev3 transgene restored their outgrowth. Moreover, Rev3 transgene expression suppressed the apoptosis in E7.5 Rev3(-/-) embryos. The Rev3(-/-) embryonic lethality, however, was not rescued by either Rev3 transgene expression or p53 deficiency. These results reveal an essential role for REV3 in the survival and growth of mammalian cells and suggest that Rev3(-/-) embryonic death occurs in a p53-independent pathway. 相似文献
74.
75.
76.
Tanaka Kenya Shimakawa Ginga Tabata Hiro Kusama Shoko Miyake Chikahiro Nakanishi Shuji 《Photosynthesis research》2021,149(1-2):57-68
Photosynthesis Research - Plants in their natural environment are often exposed to fluctuating light because of self-shading and cloud movements. As changing frequency is a key characteristic of... 相似文献
77.
Rie Nishikawa-Shimono Yoshinori Sekiguchi Takeshi Koami Madoka Kawamura Daisuke Wakasugi Kazuhito Watanabe Shunichi Wakahara Kayo Kimura Susumu Yamanobe Tetsuo Takayama 《Bioorganic & medicinal chemistry》2013,21(24):7674-7685
In this study, we describe the synthesis and structure–activity relationship (SAR) of a series of isoquinoline chemoattractant receptor–homologous molecule expressed on Th2 cells (CRTH2) antagonists. TASP0376377 (15-20), one of the most potent compounds, showed a potent binding affinity (IC50 = 19 nM) in addition to the excellent functional antagonist activity (IC50 = 13 nM). Moreover, the efficacy of this compound in a chemotaxis assay (IC50 = 23 nM) was in good agreement with its potency as a CRTH2 antagonist. In addition, 15-20 exhibited greater selectivity in binding to CRTH2 than to the DP1 prostanoid receptor (IC50 >1 μM) or the enzymes COX-1 and COX-2 (IC50 >10 μM). 相似文献
78.
79.
Fisher LA Bessho M Wakasugi M Matsunaga T Bessho T 《Journal of molecular biology》2011,413(2):337-346
Nucleotide excision repair (NER) is a very important defense system against various types of DNA damage, and it is necessary for maintaining genomic stability. The molecular mechanism of NER has been studied in considerable detail, and it has been shown that proper protein-protein interactions among NER factors are critical for efficient repair. A structure-specific endonuclease, XPF-ERCC1, which makes the 5′ incision in NER, was shown to interact with a single-stranded DNA binding protein, RPA. However, the biological significance of this interaction was not studied in detail. We used the yeast two-hybrid assay to determine that XPF interacts with the p70 subunit of RPA. To further examine the role of this XPF-p70 interaction, we isolated a p70-interaction-deficient mutant form of XPF that contains a single amino acid substitution in the N-terminus of XPF by the reverse yeast two-hybrid assay using randomly mutagenized XPF. The biochemical properties of this RPA-interaction-deficient mutant XPF-ERCC1 are very similar to those of wild-type XPF-ERCC1 in vitro. Interestingly, expression of this mutated form of XPF in the XPF-deficient Chinese hamster ovary cell line, UV41, only partially restores NER activity and UV resistance in vivo compared to wild-type XPF. We discovered that the RPA-interaction-deficient XPF is not localized in nuclei and the mislocalization of XPF-ERCC1 prevents the complex from functioning in NER. 相似文献
80.
Fischer ES Scrima A Böhm K Matsumoto S Lingaraju GM Faty M Yasuda T Cavadini S Wakasugi M Hanaoka F Iwai S Gut H Sugasawa K Thomä NH 《Cell》2011,147(5):1024-1039
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs). The DCAF DDB2 detects UV-induced pyrimidine dimers in the genome and facilitates nucleotide excision repair. We provide the molecular basis for DDB2 receptor-mediated cyclobutane pyrimidine dimer recognition in chromatin. The structures of the fully assembled DDB1-DDB2-CUL4A/B-RBX1 (CRL4(DDB2)) ligases reveal that the mobility of the ligase arm creates a defined ubiquitination zone around the damage, which precludes direct ligase activation by DNA lesions. Instead, the COP9 signalosome (CSN) mediates the CRL4(DDB2) inhibition in a CSN5 independent, nonenzymatic, fashion. In turn, CSN inhibition is relieved upon DNA damage binding to the DDB2 module within CSN-CRL4(DDB2). The Cockayne syndrome A DCAF complex crystal structure shows that CRL4(DCAF(WD40)) ligases share common architectural features. Our data support a general mechanism of ligase activation, which is induced by CSN displacement from CRL4(DCAF) on substrate binding to the DCAF. 相似文献