全文获取类型
收费全文 | 1168篇 |
免费 | 134篇 |
国内免费 | 1篇 |
出版年
2022年 | 3篇 |
2021年 | 24篇 |
2020年 | 8篇 |
2019年 | 14篇 |
2018年 | 15篇 |
2017年 | 21篇 |
2016年 | 38篇 |
2015年 | 57篇 |
2014年 | 52篇 |
2013年 | 70篇 |
2012年 | 90篇 |
2011年 | 67篇 |
2010年 | 59篇 |
2009年 | 56篇 |
2008年 | 76篇 |
2007年 | 83篇 |
2006年 | 64篇 |
2005年 | 80篇 |
2004年 | 86篇 |
2003年 | 59篇 |
2002年 | 58篇 |
2001年 | 15篇 |
2000年 | 10篇 |
1999年 | 13篇 |
1998年 | 23篇 |
1997年 | 13篇 |
1996年 | 14篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1975年 | 3篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1966年 | 4篇 |
1899年 | 2篇 |
排序方式: 共有1303条查询结果,搜索用时 15 毫秒
51.
In gram-negative organisms, high-affinity transport of iron substrates requires energy transduction to specific outer membrane receptors by the TonB-ExbB-ExbD complex. Vibrio cholerae encodes two TonB proteins, one of which, TonB1, recognizes only a subset of V. cholerae TonB-dependent receptors and does not facilitate transport through Escherichia coli receptors. To investigate the receptor specificity exhibited by V. cholerae TonB1, chimeras were created between V. cholerae TonB1 and E. coli TonB. The activities of the chimeric TonB proteins in iron utilization assays demonstrated that the C-terminal one-third of either TonB confers the receptor specificities associated with the full-length TonB. Single-amino-acid substitutions near the C terminus of V. cholerae TonB1 were identified that allowed TonB1 to recognize E. coli receptors and at least one V. cholerae TonB2-dependent receptor. This indicates that the very C-terminal end of V. cholerae TonB1 determines receptor specificity. The regions of the TonB-dependent receptors involved in specificity for a particular TonB protein were investigated in experiments involving domain switching between V. cholerae and E. coli receptors exhibiting different TonB specificities. Switching the conserved TonB box heptapeptides at the N termini of these receptors did not alter their TonB specificities. However, replacing the amino acid immediately preceding the TonB box in E. coli receptors with an aromatic residue allowed these receptors to use V. cholerae TonB1. Further, site-directed mutagenesis of the TonB box -1 residue in a V. cholerae TonB2-dependent receptor demonstrated that a large hydrophobic amino acid in this position promotes recognition of V. cholerae TonB1. These data suggest that the TonB box -1 position controls productive interactions with V. cholerae TonB1. 相似文献
52.
53.
Yuan ZQ Feldman RI Sun M Olashaw NE Coppola D Sussman GE Shelley SA Nicosia SV Cheng JQ 《The Journal of biological chemistry》2002,277(33):29973-29982
Previous studies have demonstrated that AKT1 and AKT3 are activated by heat shock and oxidative stress via both phosphatidylinositol 3-kinase-dependent and -independent pathways. However, the activation and role of AKT2 in the stress response have not been fully elucidated. In this study, we show that AKT2 in epithelial cells is activated by UV-C irradiation, heat shock, and hyperosmolarity as well as by tumor necrosis factor alpha (TNFalpha) through a phosphatidylinositol 3-kinase-dependent pathway. The activation of AKT2 inhibits UV- and TNF alpha-induced c-Jun N-terminal kinase (JNK) and p38 activities that have been shown to be required for stress- and TNF alpha-induced programmed cell death. Moreover, AKT2 interacts with and phosphorylates I kappa B kinase alpha. The phosphorylation of I kappa B kinase alpha and activation of NF kappa B mediates AKT2 inhibition of JNK but not p38. Furthermore, phosphatidylinositol 3-kinase inhibitor or dominant negative AKT2 significantly enhances UV- and TNF alpha-induced apoptosis, whereas expression of constitutively active AKT2 inhibits programmed cell death in response to UV and TNFalpha -induced apoptosis by inhibition of stress kinases and provide the first evidence that AKT inhibits stress kinase JNK through activation of the NF kappa B pathway. 相似文献
54.
55.
The SfiI endonuclease is a tetrameric protein with two DNA-binding clefts. It has to bind two copies of its recognition sequence, one at each cleft, before it cleaves DNA. While SfiI binds cooperatively to two cognate sites, it binds only one non-cognate DNA molecule at a time and the resultant complex is precluded from binding cognate DNA at the vacant cleft. To examine the communications between separate binding sites in a protein that synapses two segments of DNA, SfiI was tested with oligonucleotide duplexes containing its recognition sequence but with either R(p) or S(p) phosphorothioate linkages at the scissile bonds. Though SfiI has low activity on the R(p) and none against the S(p) diastereoisomer, it bound these duplexes in the same cooperative manner as oxyester duplexes, though with a reduced affinity for the S(p) derivative. It also formed complexes with one phosphorothioate-duplex and one oxyester-duplex but, when Mg(2+) was added to the hybrid complexes, the phosphorothioate moiety at one DNA-binding cleft prevented the enzyme from cleaving the oxyester duplex at the other cleft. SfiI is thus restrained from catalytic action until it recognises the correct nucleotide sequence at two DNA loci and the correct phosphodiester functions at both loci. 相似文献
56.
57.
58.
The prevalence and intensity of the hematophagous pennellid copepod Haemobaphes diceraus were monitored over a 10-mo period in shiner perch Cymatogaster aggregata at Pipers Lagoon, Nanaimo, British Columbia. The prevalence and mean intensity of metamorphosed adult female H. diceraus (n = 421) were 10.0% and 1.2 (+/-0.5 SD), respectively. The majority (97.9%) of infected fish had single infections, reflecting the possibility of intensity-dependent parasite-induced mortality, rejection of additional parasites, or both. Transforming females were detected throughout the year; however, there was no detectable seasonal pattern of colonization. Neither copepodids nor adult males of H. diceraus were observed on the gills of shiner perch, and this was consistent with the hypothesis that an intermediate host harbors these stages. Males of Haemobaphes sp. infected the gills of bay pipefish Syngnathus griseolineatus with a prevalence and mean intensity of 56.0% and 6.8 +/- 3.7, respectively. Transmission of H. diceraus to shiner perch probably occurs in inshore protected areas, where shiner perch ecologically overlap with the probable intermediate host of H. diceraus, the bay pipefish. 相似文献
59.
60.
The Ran GTPase system in fission yeast affects microtubules and cytokinesis in cells that are competent for nucleocytoplasmic protein transport
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Misregulation of the evolutionarily conserved GTPase Ran in fission yeast results in defects in several cellular processes in cells that are competent for nucleocytoplasmic protein transport. These results suggest that transport is neither the only nor the primary Ran-dependent process in living cells. The ability of Ran to independently regulate multiple cellular processes in vivo is demonstrated by showing that (i) eight different transport-competent RanGEF (guanine nucleotide exchange factor) mutants have defects in mitotic spindle formation; (ii) the RanGEF temperature-sensitive mutant pim1-d1 has abnormal actin ring structures at the septum. Overexpression of Imp2p, which specifically destabilizes these structures, restores viability. (iii) Ran-dependent processes differ in their requirements for active Ran in vivo. Microtubule function, cytokinesis, and nuclear envelope structure are the Ran-dependent processes most sensitive to the amount of Ran protein in the cell, whereas nucleocytoplasmic protein transport is the most robust. Therefore, the ability of Ran from Schizosaccharomyces pombe to independently regulate multiple cellular processes may reflect differences in its interactions with the binding proteins that mediate these functions and explain the complex phenotypic consequences of its misregulation in vivo. 相似文献