全文获取类型
收费全文 | 828篇 |
免费 | 67篇 |
国内免费 | 3篇 |
出版年
2023年 | 7篇 |
2022年 | 11篇 |
2021年 | 24篇 |
2020年 | 6篇 |
2019年 | 17篇 |
2018年 | 22篇 |
2017年 | 19篇 |
2016年 | 22篇 |
2015年 | 31篇 |
2014年 | 38篇 |
2013年 | 46篇 |
2012年 | 50篇 |
2011年 | 55篇 |
2010年 | 42篇 |
2009年 | 35篇 |
2008年 | 46篇 |
2007年 | 44篇 |
2006年 | 29篇 |
2005年 | 26篇 |
2004年 | 30篇 |
2003年 | 33篇 |
2002年 | 19篇 |
2001年 | 14篇 |
2000年 | 21篇 |
1999年 | 11篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 5篇 |
1992年 | 12篇 |
1991年 | 10篇 |
1989年 | 8篇 |
1988年 | 9篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 15篇 |
1984年 | 6篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1972年 | 5篇 |
1967年 | 5篇 |
1966年 | 5篇 |
排序方式: 共有898条查询结果,搜索用时 15 毫秒
41.
Coupling of conformational folding and disulfide-bond reactions in oxidative folding of proteins 总被引:6,自引:0,他引:6
The oxidative folding of proteins consists of conformational folding and disulfide-bond reactions. These two processes are coupled significantly in folding-coupled regeneration steps, in which a single chemical reaction (the "forward" reaction) converts a conformationally unstable precursor species into a conformationally stable, disulfide-protected successor species. Two limiting-case mechanisms for folding-coupled regeneration steps are described. In the folded-precursor mechanism, the precursor species is preferentially folded at the moment of the forward reaction. The (transient) native structure increases the effective concentrations of the reactive thiol and disulfide groups, thus favoring the forward reaction. By contrast, in the quasi-stochastic mechanism, the forward reaction occurs quasi-stochastically in an unfolded precursor; i.e., reactive groups encounter each other with a probability determined primarily by loop entropy, albeit modified by conformational biases in the unfolded state. The resulting successor species is initially unfolded, and its folding competes with backward chemical reactions to the unfolded precursors. The folded-precursor and quasi-stochastic mechanisms may be distinguished experimentally by the dependence of their kinetics on factors affecting the rates of thiol--disulfide exchange and conformational (un)folding. Experimental data and structural and biochemical arguments suggest that the quasi-stochastic mechanism is more plausible than the folded-precursor mechanism for most proteins. 相似文献
42.
This study, spread over a span of 2 years describes Candida infections in burn patients of an Indian hospital. A total of 220 burn patients were monitored and Candida could be isolated from 138 patients. A total of 228 different Candida species were obtained from various body locations of these patients. Species identification revealed that Candida albicans was the most predominant (45) followed by Candida tropicalis(33), Candida glabrata (13.5), C. parapsilosis (4), C. krusei (2.75) and C. kefyr (1.75). DNA fingerprinting of all C. albicans isolates was done by using CARE-2 probe. Fingerprinting analyses of all the C. albicans strains revealed that strains collected from different patients were different. It is noteworthy that patients with disseminated
candidiasis had a similar, but unique strain isolated from all body locations, suggesting a possibility that commensal isolates
might be turning pathogenic. Taken together, this is probably the first ever detailed survey of Candidainfections in burn patients in India and is expected to lead to better clinical management of this group of patients. 相似文献
43.
In the present study, we investigated the mechanisms by which zinc causes growth arrest in colon cancer cells. The results suggest that zinc treatment stabilizes the levels of the wild-type adenomatous polyposis coli (APC) protein at the post-translational level since the APC mRNA levels and the promoter activity of the APC gene were decreased in HCT-116 cells (which express the wild-type APC gene) after treatment with ZnCl2. Increased levels of wild-type but not truncated APC proteins were required for the ZnCl2-mediated G2/M phase arrest in different colon cancer cell lines. We further tested whether serum-stimulation, which induces cell cycle arrest in the S phase, can relieve ZnCl2-induced G2/M phase arrest of HCT-116 cells. Results showed that in the HCT-116 cells pretreated with ZnCl2, the serum-stimulation neither changed the distribution of G2/M phase arrested cells nor the increased levels of APC protein. The G2/M phase arrest correlated with retarded growth of HCT-116 cells. To further establish that wild-type APC protein plays a role in ZnCl2-induced G2/M arrest, we treated SW480 colon cancer cells that express truncated APC protein. We found that ZnCl2 treatment did not induce G2/M phase arrest in SW480 cells; however, the cell growth was retarded due to the loss of E-cadherin and alpha-tubulin levels. These results suggest that ZnCl2 inhibits the proliferation of colon cancer cells (which carry the wild-type APC gene) through stabilization of the APC protein and cell cycle arrest in the G2/M phase. On the other hand, ZnCl2 inhibits the proliferation of colon cancer cells (which carry the mutant APC gene) by disrupting cellular attachment and microtubule stability. 相似文献
44.
In this report, we highlight the opto-electrical processes at a conducting polymer-bacteriorhodopsin (bR) interface in presence of a voltage bias. Oriented bR on a conducting polymer substrate forms a unique hybrid system where the oxidation state of the polymer controls the optically activated proton gradient in the bR side. The internal conversion of the intermediate deprotonated M-state and the proton transfer/transport of bR at the interface can be controlled by the electrostatic environment and leads to interesting device features in this process. 相似文献
45.
PknH, a transmembrane Hank's type serine/threonine kinase from Mycobacterium tuberculosis is differentially expressed under stress conditions 总被引:1,自引:0,他引:1
Sharma K Chandra H Gupta PK Pathak M Narayan A Meena LS D'Souza RC Chopra P Ramachandran S Singh Y 《FEMS microbiology letters》2004,238(1):107-113
46.
Bhatt AN Khan MY Bhakuni V 《Protein science : a publication of the Protein Society》2004,13(8):2184-2195
The serine hydroxymethyltransferase from Bacillus subtilis (bsSHMT) and B. stearothermophilus (bstSHMT) are both homodimers and share approximately 77% sequence identity; however, they show very different thermal stabilities and unfolding pathways. For investigating the role of N- and C-terminal domains in stability and unfolding of dimeric SHMTs, we have swapped the structural domains between bs- and bstSHMT and generated the two novel chimeric proteins bsbstc and bstbsc, respectively. The chimeras had secondary structure, tyrosine, and pyridoxal-5'-phosphate microenvironment similar to that of the wild-type proteins. The chimeras showed enzymatic activity slightly higher than that of the wild-type proteins. Interestingly, the guanidium chloride (GdmCl)-induced unfolding showed that unlike the wild-type bsSHMT, which undergoes dissociation of native dimer into monomers at low guanidium chloride (GdmCl) concentration, resulting in a non-cooperative unfolding of enzyme, its chimera bsbstc, having the C-terminal domain of bstSHMT was resistant to low GdmCl concentration and showed a GdmCl-induced cooperative unfolding from native dimer to unfolded monomer. In contrast, the wild-type dimeric bstSHMT was resistant to low GdmCl concentration and showed a GdmCl-induced cooperative unfolding, whereas its chimera bstbsc, having the C- terminal domain of bsSHMT, showed dissociation of native dimer into monomer at low GdmCl concentration and a GdmCl-induced non-cooperative unfolding. These results clearly demonstrate that the C-terminal domain of dimeric SHMT plays a vital role in stabilization of the oligomeric structure of the native enzyme hence modulating its unfolding pathway. 相似文献
47.
48.
Phosphorylation enhances mitochondrial targeting of GSTA4-4 through increased affinity for binding to cytoplasmic Hsp70 总被引:4,自引:0,他引:4
Robin MA Prabu SK Raza H Anandatheerthavarada HK Avadhani NG 《The Journal of biological chemistry》2003,278(21):18960-18970
Recently we showed that three different isoforms of cytosolic glutathione S-transferases (GST), including GSTA4-4, are also localized in the mitochondrial compartment. In this study, we have investigated the mechanism of mouse GSTA4-4 targeting to mitochondria, using a combination of in vitro mitochondrial import assay and in vivo targeting in COS cells transfected with cDNA. Our results show that the mitochondrial GSTA4-4 is more heavily phosphorylated compared with its cytosolic counterpart. Protein kinase activators (cAMP, forskolin, or phorbol-12-myristate-13-acetate) markedly increased GSTA4-4 targeting to mitochondria, whereas kinase inhibitors caused its retention in the cytosol. Immunoinhibition and immunodepletion studies showed that the Hsp70 chaperone is required for the efficient translation of GSTA4-4 as well as its translocation to mitochondria. Co-immunoprecipitation studies showed that kinase inhibitors attenuate the affinity of GSTA4-4 for cytoplasmic Hsp70 suggesting the importance of phosphorylation for binding to the chaperone. Mutational analysis show that the putative mitochondrial targeting signal resides within the C-terminal 20 amino acid residues of the protein and that the targeting signal requires activation by phosphorylation at the C-terminal-most protein kinase A (PKA) site at Ser-189 or protein kinase C (PKC) site at Thr-193. We demonstrate for the first time that PKA and PKC modulate the cytoplasmic and mitochondrial pools of GSTA4-4. 相似文献
49.
Devi RS Narayan S Mohan KV Sabitha KE Devi CS 《Indian journal of experimental biology》2003,41(11):1294-1299
Effect of polyherbal formulation Ambrex was evaluated in butylated hydroxytoluene (BHT) induced toxicity of lungs and liver in rats. Toxicity was produced by administering BHT (500 mg/kg/day) for 3 days. Lung damage was evidenced by elevated levels of broncho alveolar lavage fluid (BAL) parameters such as protein, lactate, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and glucose-6-phosphate dehydrogenase (G6PDH). Liver damage was proved by elevated levels of serum protein and markers such as LDH, ALP, aspartate amino transferase (AST), alanine amino transferase (ALT), decreased level of lipid peroxides (LPO) in serum and glutathione (GSH) in liver. Administration of aqueous suspension of Ambrex (50 mg/kg orally) retained these elevated levels of BAL-protein, lactate, LDH, ALP, ACP, G6PDH and serum-protein, LDH, ALP, AST and ALT at near normal values. Decreased level of liver GSH was retained at near normalcy in Ambrex pretreated BHT-administered animals. There was no change in liver LPO in all the four groups. 相似文献
50.