全文获取类型
收费全文 | 217篇 |
免费 | 29篇 |
国内免费 | 1篇 |
出版年
2021年 | 4篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 6篇 |
2015年 | 5篇 |
2014年 | 6篇 |
2013年 | 6篇 |
2012年 | 9篇 |
2011年 | 7篇 |
2010年 | 12篇 |
2009年 | 10篇 |
2008年 | 14篇 |
2007年 | 9篇 |
2006年 | 9篇 |
2005年 | 9篇 |
2004年 | 6篇 |
2003年 | 13篇 |
2002年 | 3篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 11篇 |
1997年 | 10篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1988年 | 1篇 |
1987年 | 5篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 6篇 |
1973年 | 3篇 |
1971年 | 1篇 |
1970年 | 6篇 |
1969年 | 4篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有247条查询结果,搜索用时 340 毫秒
61.
Stok JE Goloshchapov A Song C Wheelock CE Derbel MB Morisseau C Hammock BD 《Archives of biochemistry and biophysics》2004,430(2):247-255
Carboxylesterases are enzymes that catalyze the hydrolysis of ester and amide moieties. These enzymes have an active site that is composed of a nucleophile (Ser), a base (His), and an acid (Glu) that is commonly known as a catalytic triad. It has previously been observed that the majority of carboxylesterases and lipases contain a second conserved serine in their active site [Proteins, 34 (1999) 184]. To investigate whether this second serine is also involved in the catalytic mechanism, it was mutated to an alanine, a glycine or a cysteine. Site-directed mutagenesis of this conserved serine resulted in a loss of specific activity, in both the S247G and S247A mutants (5- to 15-fold), which was due to a decrease in the rate of catalysis (kcat). Due to the instability of the S247C mutant no reliable data could be attained. A carbamate inhibitor, carbaryl, was then employed to investigate whether this decrease in the kcat was due to the rate of formation of the acyl-enzyme intermediate (k2) or the rate of deacylation (k3). The S247A mutant was found only to alter k2 (2.5-fold decrease), with no effect on k3. Together with information inferred from a human carboxylesterase crystal structure, it was concluded that this serine provides an important structural support for the spatial orientation of the glutamic acid, stabilizing the catalytic triad so that it can perform the hydrolysis. 相似文献
62.
Wheelock CE Wheelock AM Zhang R Stok JE Morisseau C Le Valley SE Green CE Hammock BD 《Analytical biochemistry》2003,315(2):208-222
Carboxylesterases hydrolyze many pharmaceuticals and agrochemicals and have broad substrate selectivity, requiring a suite of substrates to measure hydrolytic profiles. To develop new esterase substrates, a series of alpha-cyanoesters that yield fluorescent products upon hydrolysis was evaluated for use in carboxylesterase assays. The use of these substrates as surrogates for Type II pyrethroid hydrolysis was tested. The results suggest that these novel analogs are appropriate for the development of high-throughput assays for pyrethroid hydrolase activity. A set of human liver microsomes was then used to determine the ability of these substrates to report esterase activity across a small population. Results were compared against standard esterase substrates. A number of the esterase substrates showed correlations, demonstrating the broad substrate selectivity of these enzymes. However, for several of the substrates, no correlations in hydrolysis rates were observed, suggesting that multiple carboxylesterase isozymes are responsible for the array of substrate hydrolytic activity. These new substrates were then compared against alpha-naphthyl acetate and 4-methylumbelliferyl acetate for their ability to detect hydrolytic activity in both one- and two-dimensional native electrophoresis gels. Cyano-2-naphthylmethyl butanoate was found to visualize more activity than either commercial substrate. These applications demonstrate the utility of these new substrates as both general and pyrethroid-selective reporters of esterase activity. 相似文献
63.
Differential displacement of classical cadherins by VE-cadherin 总被引:5,自引:0,他引:5
VE-cadherin is an endothelial cell-specific, type II classical cadherin that plays an important role in permeability, vasculogenesis, and vascular remodeling. Endothelial cells express equal levels of VE- and N-cadherin; VE-cadherin is present injunctions while N-cadherin is diffusely expressed over the surface of the cell. The present study was designed first to determine if the ability of VE-cadherin to displace N-cadherin from junctions was endothelial-cell specific, and second to determine if VE-cadherin could displace other classical cadherins from cell junctions. Our data suggest that VE-cadherin specifically influences the cellular localization of N-cadherin, independent of cell type, and does not effect the localization of other classical cadherins. 相似文献
64.
65.
66.
Wingfield BD; Grant WS; Wolfaardt JF; Wingfield MJ 《Molecular biology and evolution》1994,11(3):376-383
The genus Ceratocystis sensu stricto includes important fungal pathogens of
woody and herbaceous plants. This genus is distinguished from species in
Ceratocystis sensu lato by the presence of Chalara anamorphs. Ascospore
shape has been used extensively in delineating Ceratocystis taxa, which
show a large variety of ascospore shapes. Sequence analysis of one region
of he 18S ribosomal RNA subunit and two regions of the 28S ribosomal RNA
subunit showed that there was a majority of multiple substitutions at
nucleotide sites and that there was a low transition/transversion ratio, T
= 0.72. Both of these results suggest that these are well established, old
species. Ascospore morphology, for the most part, was not congruent with
the molecular phylogeny, and the use of morphological characters may be
misleading in the taxonomy of these species.
相似文献
67.
It was previously reported that the establishment of the L5178Y cell tumor-dormant state in DBA/2 mice is mediated principally by a peritoneal cytolytic T-cell response that reaches peak levels 4 days after L5178Y cell challenge, lyses more than 99% but less than 100% of peritoneal L5178Y cells, and gradually wanes to background levels by 40–70 days postchallenge (DPC). At this time the majority of mice are clinically normal, and contain a relatively small number of L5178Y cells in the peritoneal cavity. During the tumor-dormant state, mice that harbor more than 104 L5178Y cells contain peritoneal macrophage-mediated cytolytic activity. We report here that tumor-dormant mice that contain fewer than 104 peritoneal L5178Y cells also produce cytolytic activity in vitro, but that it is synergistic, in that the cytolytic activity of adherent (AD) peritoneal cells (PEC) and nonadherent (NAD) PEC cultured together is greater than the additive lysis produced by these cell populations when cultured separately. This synergistic cytolytic activity is: (1) effector cell density dependent, (2) dependent on the tumor-dormant status of the NAD and AD PEC donor mice, (3) protracted in its kinetics during a 48-hr in vitro assay, and (4) dependent on an interaction between NAD T cells and AD phagocytic macrophages. The consistent detection of this in vitro-assayed cytolytic activity in PEC of tumor-dormant mice which harbor small endogenous tumor burdens suggests that it reflects an in vivo cytotoxic effector mechanism involved in the long-term maintenance of the tumor-dormant state. 相似文献
68.
MJ Doughty 《Biotechnic & histochemistry》2016,91(8):501-509
Goblet cells were visualized in impression cytology specimens from bulbar conjunctiva of the rabbit eye using Giemsa staining. Highly magnified images were used to generate outlines of the goblet cells and their characteristic eccentric nuclei. Using sets of 10 cells from 15 cytology specimens, I found that the longest dimension of the goblet cells averaged 16.7 ± 2.3 μm, the shortest dimension averaged 14.4 ± 1.8 μm and the nucleus averaged 6.3 ± 0.8 μm. The goblet cells were ellipsoid in shape and the longest:shortest cell dimension ratio averaged 1.169 ± 0.091. The goblet cell areas ranged from 108 to 338 μm2 (average 193 ± 50 μm2). The area could be predicted reliably from the longest and shortest dimensions (r2 = 0.903). The areas of goblet cell nuclei were 15–58 μm2 (average 33 ± μm2) and the nucleus:cytoplasm area fraction was predictably greater in smaller goblet cells and less in the larger goblet cells (Spearman correlation = 0.817). The nuclei were estimated to occupy an average of 9.5% of the cell volume. The differences in size, shape and nucleus:cytoplasm ratio may reflect differences in goblet cell maturation. 相似文献
69.
While characterizing various splice forms of p120 catenin, we observed what appeared to be a novel posttranslational modification of p120, resulting in a higher molecular weight form that was dependent on the splicing pattern. Further investigation revealed the higher molecular weight form to be a fusion protein between sequences encoded by the retroviral vector and p120. We found that the publicly available sequence of the vector we used does not agree with the experimental sequence. We caution other investigators to be aware of this potential artifact. 相似文献
70.