全文获取类型
收费全文 | 377篇 |
免费 | 46篇 |
专业分类
423篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 11篇 |
2015年 | 26篇 |
2014年 | 15篇 |
2013年 | 19篇 |
2012年 | 34篇 |
2011年 | 25篇 |
2010年 | 18篇 |
2009年 | 18篇 |
2008年 | 23篇 |
2007年 | 25篇 |
2006年 | 22篇 |
2005年 | 20篇 |
2004年 | 18篇 |
2003年 | 17篇 |
2002年 | 17篇 |
2001年 | 12篇 |
2000年 | 16篇 |
1999年 | 10篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 6篇 |
1992年 | 8篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
排序方式: 共有423条查询结果,搜索用时 15 毫秒
31.
With PCR products as probes, we have cloned two new cry-type genes from Bacillus thuringiensis subsp. wuhanensis. The deduced amino acid sequence of the first clone is 77.3% identical to Cry1Ga1. The deduced protein sequence of the second
clone is 69.8–78.7% identical to that of Cry1B group. The nomenclature assignment of these two clones is, therefore, named
Cry1Gb1 and Cry1Bd1, respectively. The Cry1Bd1 is toxic to Plutella xylostella larvae, and the Cry1Gb1 is toxic to Pieris rapae larvae.
Received: 2 August 1999 / Accepted: 18 October 1999 相似文献
32.
Ingoglia NA Ramanathan M Zhang N Tzeng B Mathur G Opuni K Donnelly R 《Neurochemical research》2000,25(1):51-58
The N-terminal, posttranslational arginylation of proteins is ubiquitous in eukaryotic cells. Previous experiments, using purified components of the reaction incubated in the presence of exogenous substrates, have shown that only those proteins containing acidic residues at their N-terminals are arginylation substrates. However, data from experiments that used crude extracts of brain and nerve as the source of the arginylating molecules, suggest that the in vivo targets for arginylation are more complex than those demonstrated using purified components. One of the proposed functions for arginylation is as a signal for protein degradation and proteins that have undergone oxidative damage have been shown to be rapidly degraded. In the present experiments we have tested the hypothesis that the presence of an oxidatively damaged residue in a protein is a signal for its arginylation. These experiments have been performed by adding synthetic oxidized peptides to crude extracts of rat brain, incubating them with [3H]Arg and ATP and assaying for arginylated peptides using RP-HPLC. Results showed that while the oxidized A-chain of insulin was arginylated in this system, confirming previous experiments, other peptides containing oxidized residues were not. When a peptide containing Glu in the N-terminus was incubated under the same conditions it too was not a substrate for arginylation. These findings show that neither the presence of an N-terminal acidic residue nor an oxidized residue alone are sufficient to signal arginylation. Thus, another feature of the oxidized A-chain of insulin is required for arginylation. That feature remains to be identified. 相似文献
33.
Novel Assay Reveals Multiple Pathways Regulating Stress-Induced Accumulations of Inorganic Polyphosphate in Escherichia coli 总被引:3,自引:0,他引:3 下载免费PDF全文
Dana Ault-Rich Cresson D. Fraley Chi-Meng Tzeng Arthur Kornberg 《Journal of bacteriology》1998,180(7):1841-1847
A major impediment to understanding the biological roles of inorganic polyphosphate (polyP) has been the lack of sensitive definitive methods to extract and quantitate cellular polyP. We show that polyP recovered in extracts from cells lysed with guanidinium isothiocynate can be bound to silicate glass and quantitatively measured by a two-enzyme assay: polyP is first converted to ATP by polyP kinase, and the ATP is hydrolyzed by luciferase to generate light. This nonradioactive method can detect picomolar amounts of phosphate residues in polyP per milligram of extracted protein. A simplified procedure for preparing polyP synthesized by polyP kinase is also described. Using the new assay, we found that bacteria subjected to nutritional or osmotic stress in a rich medium or to nitrogen exhaustion had large and dynamic accumulations of polyP. By contrast, carbon exhaustion, changes in pH, temperature upshifts, and oxidative stress had no effect on polyP levels. Analysis of Escherichia coli mutants revealed that polyP accumulation depends on several regulatory genes, glnD (NtrC), rpoS, relA, and phoB. 相似文献
34.
Inhibition of protein synthesis by nitric oxide correlates with cytostatic activity: nitric oxide induces phosphorylation of initiation factor eIF-2 alpha. 总被引:7,自引:0,他引:7 下载免费PDF全文
Y. M. Kim K. Son S. J. Hong A. Green J. J. Chen E. Tzeng C. Hierholzer T. R. Billiar 《Molecular medicine (Cambridge, Mass.)》1998,4(3):179-190
BACKGROUND: Nitric oxide (NO) is cytostatic for proliferating cells, inhibits microbial growth, and down-regulates the synthesis of specific proteins. Studies were undertaken to determine the mechanism by which NO inhibits total protein synthesis and whether the inhibition correlates with established cytostatic activities of NO. MATERIALS AND METHODS: In in vitro experiments, various cell types were exposed to NO using either donors or expression of inducible NO synthase (iNOS). The capacity of NO to suppress total protein synthesis, measured by incorporation of 35S-methionine into protein, was correlated with the capacity of NO to suppress cell proliferation, viral replication, or iNOS expression. Phosphorylation of eIF-2 alpha was examined as a possible mechanism for the suppressed protein synthesis by NO. RESULTS: Both NO donors and expression of the iNOS suppressed total protein synthesis in L929 cells and A2008 human ovarian tumor cells in parallel with decreased cell proliferation. Suppressed protein synthesis was also shown to correlate with decreased vaccinia virus proliferation in murine peritoneal macrophages in an iNOS-dependent manner. Furthermore, iNOS expression in pancreatic islets or RAW264.7 cells almost completely inhibited total protein synthesis, suggesting that nonspecific inhibition of protein synthesis may be the mechanism by which NO inhibited the synthesis of specific proteins such as insulin or iNOS itself. This possibility was confirmed in RAW264.7 cells where the inhibition of total protein synthesis correlated with the decreased iNOS protein. The decrease in protein levels occurred without changes in iNOS mRNA levels, implicating an inhibition of translation. Mechanistic studies revealed that iNOS expression in RAW264.7 cells resulted in the phosphorylation of eIF-2 alpha and inhibition of the 80S ribosomal complex formation. CONCLUSIONS: These results suggest that NO suppresses protein synthesis by stimulating the phosphorylation of eIF-2 alpha. Furthermore, our observations indicate that nonspecific inhibition of protein synthesis may be a generalized response of cells exposed to high levels of NO and that inhibition of protein synthesis may contribute to many of the described cytostatic actions of NO. 相似文献
35.
Kuan-Min Fang Chung-Shi Yang†‡ Synthia H. Sun§ Shun-Fen Tzeng 《Journal of neurochemistry》2009,111(5):1225-1237
Microglia, the CNS resident macrophages responsible for the clearance of degenerating cellular fragments, are essential to tissue remodeling and repair after CNS injury. ATP can be released in large amounts after CNS injury and may mediate microglial activity through the ionotropic P2X and the metabotropic P2Y receptors. This study indicates that exposure to a high concentration of ATP for 30 min rapidly induces changes of the microglial cytoskeleton, and significantly attenuates microglial phagocytosis. A pharmacological approach showed that ATP-induced inhibition of microglial phagocytotic activity was due to P2X7 R activation, rather than that of P2YR. Activation of P2X7 R by its agonist, 2'-3'- O -(4-benzoyl)benzoyl-ATP (BzATP), produced a Ca2+ -independent reduction in microglial phagocytotic activity. In addition, the knockdown of P2X7 R expression by lentiviral-mediated shRNA interference or the blockade of P2X7 R activation by the specific antagonists, oxidized ATP (oxATP) and brilliant blue G, has efficiently restored the phagocytotic activity of ATP and BzATP-treated microglia. Our results reveal that P2X7 R activation may induce the formation of a Ca2+ -independent signaling complex, which results in the reduction of microglial phagocytosis. This suggests that exposure to ATP for a short-term period may cause insufficient clearance of tissue debris by microglia through P2X7 R activation after CNS injury, and that blockade of this receptor may preserve the phagocytosis of microglia and facilitate CNS tissue repair. 相似文献
36.
37.
38.
Peng HK Lin CK Yang SY Tseng CK Tzeng CC Lee JC Yang SC 《Bioorganic & medicinal chemistry letters》2012,22(2):1107-1110
Hepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. Here, we have synthesized a series of anilinoquinoline derivatives. Based on a cell-based HCV replicon system, we observed that 2-(3'-nitroanilino)quinoline (18) exhibited anti-HCV activity with a 50% effective concentration (EC(50)) value of 7μM and a selective index (SI) value of 10. In addition, compound 18 possessed the inhibitory effect on HCV NS3/4A protease activity. Therefore, we concluded that the compound 18 possessed a potent activity against HCV replication and could provide as a new lead compound as anti-HCV inhibitor. 相似文献
39.
Chih-Hua Tseng Chang-Sheng Lin Pin-Keng Shih Lo-Ti Tsao Jih-Pyang Wang Chih-Mei Cheng Cherng-Chyi Tzeng Yeh-Long Chen 《Bioorganic & medicinal chemistry》2009,17(18):6773-6779
Synthesis and anti-inflammatory effects of certain furo[3′,2′:3,4]naphtho[1,2-d]imidazole derivatives 12–18 were studied. These compounds were synthesized from naphtho[1,2-b]furan-4,5-dione (10) which in turn was prepared from the known 2-hydoxy-1,4-naphthoquinone (7) in a one pot reaction. Furo[3′,2′:3,4]naphtho[1,2-d]imidazole (12) was inactive (IC50 value of >30 μM) while its 5-phenyl derivative 13, with an IC50 value of 16.3 and 11.4 μM against lysozyme and β-glucuronidase release, respectively, was comparable to the positive trifluoperazine. The same potency was observed for 5-furan derivative 16 with an IC50 value of 19.5 and 11.3 μM against lysozyme and β-glucuronidase release, respectively. An electron-withdrawing NO2 substituted on 5-phenyl or 5-furanyl group led to the devoid of activity as in the cases of 14 and 17. Among them, compound 15 exhibited significant inhibitory effects, with an IC50 value of 7.4 and 5.0 μM against lysozyme and β-glucuronidase release, respectively.For the LPS-induced NO production, the phenyl derivatives 12–15 were inactive while the nitrofuran counterparts 17 and 18 suppress LPS-induced NO production significantly, with an IC50 value of 1.5 and 1.3 μM, respectively, which are more active than that of the positive 1400 W. Compounds 16–18 were capable of inhibiting LPS-induced iNOS protein expression at a dose-dependent manner in which compound 18, with an IC50 of 0.52 μM in the inhibition of iNOS expression, is approximately fivefold more potent than that of the positive 1400 W. In the CLP rat animal model, compound 18 was found to be more active than the positive hydrocortisone in the inhibition of the iNOS mRNA expression in rat lung tissue. The sepsis-induced PGE2 production in rat serum decreased 150% by the pretreatment of 18 in a dose of 10 mg/kg. 相似文献
40.
Yerra Koteswara Rao Te-Yu Kao Ming-Fang Wu Jiunn-Liang Ko Yew-Min Tzeng 《Bioorganic & medicinal chemistry》2010,18(19):6987-6994