全文获取类型
收费全文 | 381篇 |
免费 | 62篇 |
国内免费 | 17篇 |
出版年
2023年 | 4篇 |
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 9篇 |
2013年 | 13篇 |
2012年 | 17篇 |
2011年 | 11篇 |
2010年 | 15篇 |
2009年 | 16篇 |
2008年 | 15篇 |
2007年 | 14篇 |
2006年 | 13篇 |
2005年 | 17篇 |
2004年 | 9篇 |
2003年 | 16篇 |
2002年 | 16篇 |
2001年 | 13篇 |
2000年 | 16篇 |
1999年 | 13篇 |
1998年 | 7篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 13篇 |
1991年 | 11篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 5篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1979年 | 5篇 |
1978年 | 10篇 |
1977年 | 9篇 |
1976年 | 4篇 |
1973年 | 3篇 |
1971年 | 4篇 |
1967年 | 2篇 |
排序方式: 共有460条查询结果,搜索用时 15 毫秒
41.
Budding of C-type retroviruses begins when the viral Gag polyprotein is directed to the plasma membrane by an N-terminal membrane-binding (M) domain. While dispersed basic amino acids within the M domain are critical for stable membrane association and consequent particle assembly, additional residues or motifs may be required for specific plasma membrane targeting and binding. We have identified an assembly-defective Rous sarcoma virus (RSV) Gag mutant that retains significant membrane affinity despite having a deletion of the fourth alpha-helix of the M domain. Examination of the mutant protein's subcellular distribution revealed that it was not localized to the plasma membrane but instead was mistargeted to intracytoplasmic membranes. Specific plasma membrane targeting was restored by the addition of myristate plus a single basic residue, by multiple basic residues, or by the heterologous hydrophobic membrane-binding domain from the cellular Fyn protein. These results suggest that the fourth alpha-helix of the RSV M domain promotes specific targeting of Gag to the plasma membrane, either through a direct interaction with plasma membrane phospholipids or a membrane-associated cellular factor or by maintaining the conformation of Gag to expose specific plasma membrane targeting sequences. 相似文献
42.
Calmodulin (CaM) is a major cellular sensor of calcium signaling, interacts with numerous proteins associated with cellular second messenger systems (e.g., cyclic AMP, nitric oxide), and is associated with neurosecretory activity. An identical CaM protein consisting of four helix-loop-helix regions that arose by gene duplication is encoded by three nonallelic mammalian genes that are some of the most highly conserved genes known. Differential tissue and cellular expression of each CaM suggest unique functions that promote strong selective preservation of these replicate, yet distinct, CaM genes in mammals. Each gene displays the same exon-intron arrangement but is characterized by distinct promoter elements and by unique 5'- and 3'-untranslated regions that are highly conserved among human, rat, and mouse. These distinct untranslated regions may permit regulation of CaM levels at discrete cellular sites during differentiation and in highly specialized cell types such as neurons. 相似文献
43.
Carlisle R Rhoads CA Aw TY Harrison L 《American journal of physiology. Cell physiology》2002,283(6):C1675-C1686
Human umbilical vein endothelial cells (HUVECs) are an endothelial model of replicative senescence. Oxidative stress, possibly due to dysfunctional mitochondria, is believed to play a key role in replicative senescence and atherosclerosis, an age-related vascular disease. In this study, we determined the effect of cell division on genomic instability, mitochondrial function, and redox status in HUVECs that were able to replicate for approximately 60 cumulative population doublings (CPD). After 20 CPD, the nuclear genome deteriorated and the protein content of the cell population increased. This indicated an increase in cell size, which was accompanied by an increase in oxygen consumption, ATP production, and mitochondrial genome copy number and approximately 10% increase in mitochondrial mass. The antioxidant capacity increased, as seen by an increase in reduced glutathione, glutathione peroxidase, GSSG reductase, and glucose-6-phosphate dehydrogenase. However, by CPD 52, the latter two enzymes decreased, as well as the ratio of mitochondrial-to-nuclear genome copies, the mitochondrial mass, and the oxygen consumption per milligram of protein. Our results signify that HUVECs maintain a highly reducing (GSH) environment as they replicate despite genomic instability and loss of mitochondrial function. 相似文献
44.
Dietary oxidants like lipid hydroperoxides (LOOH) can perturb cellular glutathione/glutathione disulphide (GSH/GSSG) status and disrupt mucosal turnover. This study examines the effect of LOOH on GSH/GSSG balance and phase transitions in the human colon cancer CaCo-2 cell. LOOH at 1 or 5 micro m were noncytotoxic, but disrupted cellular GSH/GSSG and stimulated proliferative activity at 6 h that paralleled increases in ornithine decarboxylase activity, thymidine incorporation, expression of cyclin D1/cyclin-dependent kinase 4, phosphorylation of retinoblastoma protein, and cell progression from G0/G1 to S. At 24 h, LOOH-induced sustained GSH/GSSG imbalance mediated growth arrest at G0/G1 that correlated with suppression of proliferative activity and enhanced oxidative DNA damage. LOOH-induced cell transitions were effectively blocked by N-acetylcysteine. Collectively, the study shows that subtoxic LOOH levels induce CaCo-2 GSH/GSSG imbalance that elicits time-dependent cell proliferation followed by growth arrest. These results provide insights into the mechanism of hydroperoxide-induced disruption of mucosal turnover with implications for understanding oxidant-mediated genesis of gut pathology. 相似文献
45.
Zuberek J Jemielity J Stepinski J Lewdorowicz M Niedzwiecka A Haber D Stolarski R Rhoads RE Darzynkiewicz E 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):1703-1706
Studies on the interaction of the murine translation initiation factor 4E with two new-synthesized cap-analogues, modified at C2' of 7-methylguanosine, have been performed by means of the fluorescence titration method. No difference in the binding affinity for eIF4E was observed compared with the "anti reversed" cap analogues, possessing the analogous modifications at C3'. Potential significance of the novel caps as research tools for examination of the nuclear cap binding complex CBC80/20 has been discussed. 相似文献
46.
Mutually cooperative binding of eukaryotic translation initiation factor (eIF) 3 and eIF4A to human eIF4G-1 总被引:5,自引:0,他引:5
Korneeva NL Lamphear BJ Hennigan FL Rhoads RE 《The Journal of biological chemistry》2000,275(52):41369-41376
Eukaryotic translation initiation factor 4G-1 (eIF4G) plays a critical role in the recruitment of mRNA to the 43 S preinitiation complex. The central region of eIF4G binds the ATP-dependent RNA helicase eIF4A, the 40 S binding factor eIF3, and RNA. In the present work, we have further characterized the binding properties of the central region of human eIF4G. Both titration and competition experiments were consistent with a 1:1 stoichiometry for eIF3 binding. Surface plasmon resonance studies showed that three recombinant eIF4G fragments corresponding to amino acids 642-1560, 613-1078, and 975-1078 bound eIF3 with similar kinetics. A dissociation equilibrium constant of approximately 42 nm was derived from an association rate constant of 3.9 x 10(4) m(-1) s(-1) and dissociation rate constant of 1.5 x 10(-3) s(-1). Thus, the eIF3-binding region is included within amino acid residues 975-1078. This region does not overlap with the RNA-binding site, which suggests that eIF3 binds eIF4G directly and not through an RNA bridge, or the central eIF4A-binding site. Surprisingly, the binding of eIF3 and eIF4A to the central region was mutually cooperative; eIF3 binding to eIF4G increased 4-fold in the presence of eIF4A, and conversely, eIF4A binding to the central (but not COOH-terminal) region of eIF4G increased 2.4-fold in the presence of eIF3. 相似文献
47.
A trypsin inhibitor was identified in extracts of adult Trichuris suis and culture fluids from 24-h in vitro cultivation of adult parasites. The inhibitor was isolated by acid precipitation, affinity chromatography (trypsin-agarose), and reverse phase HPLC as a single polypeptide with a molecular weight estimated at 6.6 kDa by laser desorption mass spectrometry. The purified inhibitor associated strongly with trypsin (equilibrium dissociation inhibitory constant (K(j)) of 3.07 nM) and chymotrypsin (K(j) = 24.5 nM) and was termed TsTCI. Elastase, thrombin, and factor Xa were not inhibited. The cDNA-derived amino acid sequence of the mature TsTCI consisted of 61 residues including 8 cysteine residues with a molecular mass of 6.687 kDa. The N-terminal region of TsTCI (46 residues) showed limited homology (36%) to a protease inhibitor from the hemolymph of the honeybee Apis mellifera, which is considered to be a member of the Ascaris inhibitor family. However, TsTCI did not display sequence homology with other members of this family or the distinctive cysteine residue pattern which distinguishes this family. However, similarity of a region of TsTCI (11 residues) with the reactive site regions of inhibitors from the nematodes Ascaris suum, Anisakis simplex, and Ancylostoma caninum was apparent. 相似文献
48.
49.
MORAIS PAULO AMORIM ANTÓNIO VIEIRA DA SILVA CLÁUDIA RIBEIRO TERESA COSTA SANTOS JORGE AFONSO COSTA HELOÍSA 《Journal of genetics》2015,94(3):509-512
Journal of Genetics - 相似文献
50.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)