全文获取类型
收费全文 | 448篇 |
免费 | 56篇 |
出版年
2021年 | 4篇 |
2020年 | 6篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 9篇 |
2016年 | 13篇 |
2015年 | 23篇 |
2014年 | 22篇 |
2013年 | 20篇 |
2012年 | 23篇 |
2011年 | 30篇 |
2010年 | 15篇 |
2009年 | 13篇 |
2008年 | 16篇 |
2007年 | 21篇 |
2006年 | 12篇 |
2005年 | 17篇 |
2004年 | 15篇 |
2003年 | 17篇 |
2002年 | 14篇 |
2001年 | 16篇 |
2000年 | 11篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1992年 | 11篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1974年 | 7篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 4篇 |
1968年 | 7篇 |
1966年 | 4篇 |
1965年 | 4篇 |
排序方式: 共有504条查询结果,搜索用时 15 毫秒
61.
Evidence that TET protein functions as a multimer in the inner membrane of Escherichia coli. 总被引:4,自引:1,他引:3 下载免费PDF全文
The inner membrane TET (TetA) protein, which is involved in Tn10-mediated microbial tetracycline resistance, consists of two domains, alpha and beta, both of which are needed for tetracycline resistance and efflux (M.S. Curiale, L.M. McMurry, and S.B. Levy, J. Bacteriol. 157:211-217, 1984). Since tetracycline-sensitive mutants in one domain can partially complement sensitive mutants in the other domain and since some sensitive mutants show dominance over the wild type, a multimeric structure for TET in the membrane had been suggested. We have studied this possibility by using tetA-phoA gene fusions. We fused all but the last 40 base pairs of the tetA gene with the carboxy terminus of the phoA gene for alkaline phosphatase (PhoA), whose activity requires its dimerization in the periplasm. The tetA-phoA fusion protein was under control of the tetracycline-inducible regulatory system for the tetA gene. Induction led to the synthesis of a 78,000-dalton inner membrane protein. Tetracycline resistance was expressed at reduced levels, consistent with the terminal beta domain deletion. Alkaline phosphatase activity was also present, but at low levels, suggesting that some, but not all, of the fusion proteins had their carboxy-terminal ends in the periplasm. When wild-type or mutant TET proteins were present in the same cell with the fusion protein, the tetracycline resistance level was affected (raised or lowered); however, phosphatase activity was reduced only when TET proteins with intact or near-intact beta domains were present. These findings suggest that TET functions as a multimer and that intact beta domains, on TET molecules in the heterologous multimer, either allow fewer PhoA moieties to project into the periplasm or sterically hinder PhoA moieties from dimerizing. 相似文献
62.
63.
64.
The structures of alpha 1,2-mannose containing partially processed asparagine-linked oligosaccharides on the alpha-chain of MOPC 315 IgA were characterized using specific glycosidases and acetolysis. Man6GlcNAc2, a substrate for a Golgi alpha 1,2-mannosidase, was found to be a single isomeric structure. Likewise, Man7-9GlcNAc2 were single isomers indicating an ordered sequence of removal of alpha 1,2-linked mannose residues on this murine immunoglobulin heavy chain. 相似文献
65.
Tunicamycin, an antibiotic that prevents glycosylation of glycoproteins by blocking the formation of N-acetylglucosamine-lipid intermediates, was used to study the importance of glycosylation for the secretion of immunoglobulins by mouse plasmacytoma lines that produce immunoglobulins of different classes. Biosynthetically labeled secreted and intracellular immunoglobulins were measured by immunoprecipitation assays. Tunicamycin, at a concentration of 0.5 mug/ml produced an 81% inhibition of IgM secretion by MOPC 104E plasma cells without significantly affecting the initial rate of synthesis of intracellular IgM. No increase in the intracellular degradation of nonglycosylated IgM could be demonstrated. Tunicamycin also produced a 64% average inhibition of IgA secretion by several mouse IgA-secreting plasmacytoma lines. In contrast, despite inhibiting the incorporation of D-[14C] glucosamine into newly synthesized IgG, tunicamycin only produced a 28% average inhibition of IgG secretion, which was only slightly more than the nonspecific inhibition of secretion of the normally nonglycosylated lambda2 light chains by variant MOPC 315 plasmacytomas. These data indicate that the extent of inhibition of immunoglobulin secretion produced by tunicamycin depends on the immunoglobulin class produced by the plasma cell. 相似文献
66.
Sakya SM Cheng H Lundy Demello KM Shavnya A Minich ML Rast B Dutra J Li C Rafka RJ Koss DA Li J Jaynes BH Ziegler CB Mann DW Petras CF Seibel SB Silvia AM George DM Hickman A Haven ML Lynch MP 《Bioorganic & medicinal chemistry letters》2006,16(5):1202-1206
Structure-activity relationship (SAR) studies of novel 2-[3-trifluoromethyl-5-alkyl(thio)ether pyrazo-1-yl]-5-methanesulfonyl pyridine derivatives for canine COX enzymes are described. The 4-cyano-5-alkyl ethers were found to have excellent potency and selectivity, whereas the 5-thioethers were potent but less selective than the ether analogs in a canine whole blood (CWB) COX-2 assay. 相似文献
67.
Sakya SM DeMello KM Minich ML Rast B Shavnya A Rafka RJ Koss DA Cheng H Li J Jaynes BH Ziegler CB Mann DW Petras CF Seibel SB Silvia AM George DM Lund LA St Denis S Hickman A Haven ML Lynch MP 《Bioorganic & medicinal chemistry letters》2006,16(2):288-292
Structure-activity relationship (SAR) studies of the novel 2-[3-di and trifluoromethyl-5-alkylamino pyrazo-1-yl]-5-methanesulfonyl (SO(2)Me)/sulfamoyl (SO(2)NH(2))-pyridine derivatives for canine COX enzymes are described. The studies led to the identification of 2e as lead with potent in vitro activity, selectivity, and in vivo activity in dogs and cats. 相似文献
68.
Le Diguarher T Ortuno JC Shanks D Guilbaud N Pierré A Raimbaud E Fauchère JL Hickman JA Tucker GC Casara PJ 《Bioorganic & medicinal chemistry letters》2004,14(3):767-771
A structure-activity study was performed by synthesis on N,N'-disubstitution of 3-aminobenzo[c] and [d]azepin-2-one 2 and 3 to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities. 相似文献
69.
Two multimetric indices have been developed to help address fish community (reservoir fish assemblage index [RFAI]) and individual population quality (sport fishing index [SFI]) in Tennessee River reservoirs. The RFAI, with characteristics similar to the index of biotic integrity (IBI) used in stream fish community determinations, was developed to monitor the existing condition of resident fish communities. The index, which incorporates standardized electrofishing of littoral areas and experimental gill netting for limnetic bottom-dwelling species, has been used to determine residential fish community response to various anthropogenic impacts in southeastern reservoirs. The SFI is a multimetric index designed to address the quality of the fishery for individual resident sport fish species in a particular lake or reservoir[4]. The SFI incorporates measures of fish population aspects and angler catch and pressure estimates. This paper proposes 70% of the maximum RFAI score and 10% above the average SFI score for individual species as "screening" endpoints for balanced indigenous populations (BIP) or adverse environmental impact (AEI). Endpoints for these indices indicate: (1) communities/populations are obviously balanced indigenous populations (BIP) indicating no adverse environmental impact (AEI), or are "screened out"; (2) communities/populations are considered to be potentially impacted; and (3) where the resident fish community/population should be considered adversely impacted. Suggestions are also made concerning how examination of individual metric scores can help determine the source or cause of the impact. 相似文献
70.
Klein DC Ganguly S Coon S Weller JL Obsil T Hickman A Dyda F 《Biochemical Society transactions》2002,30(4):365-373
This paper describes the role 14-3-3 proteins play in vertebrate photoneuroendocrine transduction. 14-3-3 proteins form a complex with arylalkylamine N-acetyltransferase (AANAT), the enzyme which turns melatonin production on during the day and off at night. Complex formation is triggered at night by cAMP-dependent phosphorylation of the enzyme, and results in activation and protection against proteolysis. This enhances melatonin production >10-fold. Light exposure results in dephosphorylation of the enzyme and disassociation from 14-3-3, leading to destruction and a rapid drop in melatonin production and release and circulating levels. 相似文献