全文获取类型
收费全文 | 730篇 |
免费 | 69篇 |
出版年
2020年 | 5篇 |
2019年 | 8篇 |
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 14篇 |
2015年 | 10篇 |
2014年 | 14篇 |
2013年 | 27篇 |
2012年 | 39篇 |
2011年 | 35篇 |
2010年 | 30篇 |
2009年 | 11篇 |
2008年 | 26篇 |
2007年 | 27篇 |
2006年 | 31篇 |
2005年 | 29篇 |
2004年 | 26篇 |
2003年 | 29篇 |
2002年 | 31篇 |
2001年 | 26篇 |
2000年 | 21篇 |
1999年 | 31篇 |
1998年 | 14篇 |
1997年 | 8篇 |
1996年 | 9篇 |
1994年 | 11篇 |
1993年 | 8篇 |
1992年 | 18篇 |
1991年 | 15篇 |
1990年 | 14篇 |
1989年 | 11篇 |
1988年 | 14篇 |
1987年 | 9篇 |
1986年 | 14篇 |
1985年 | 13篇 |
1984年 | 14篇 |
1983年 | 15篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 16篇 |
1978年 | 6篇 |
1977年 | 11篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1974年 | 7篇 |
1971年 | 6篇 |
1970年 | 6篇 |
1969年 | 4篇 |
1968年 | 4篇 |
排序方式: 共有799条查询结果,搜索用时 578 毫秒
691.
Essential role of conserved arginine 160 in intramolecular electron transfer in human sulfite oxidase 总被引:1,自引:0,他引:1
Feng C Wilson HL Hurley JK Hazzard JT Tollin G Rajagopalan KV Enemark JH 《Biochemistry》2003,42(42):12235-12242
Arginine 160 in human sulfite oxidase (SO) is conserved in all SO species sequenced to date. Previous steady-state kinetic studies of the R160Q human SO mutant showed a remarkable decrease in k(cat)/K(m)(sulfite) of nearly 1000-fold, which suggests that Arg 160 in human SO makes an important contribution to the binding of sulfite near the molybdenum cofactor [Garrett, R. M., Johnson, J. L., Graf, T. N., Feigenbaum, A., Rajagopalan, K. V. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 6394-6398]. In the crystal structure of chicken SO, Arg 138, the equivalent of Arg 160 in human SO, is involved in the formation of a positively charged sulfite binding site [Kisker, C., Schindelin, H., Pacheco, A., Wehbi, W., Garnett, R. M., Rajagopalan, K. V., Enemark, J. H., Rees, D. C. (1997) Cell 91, 973-983]. To further assess the role of Arg 160 in human SO, intramolecular electron transfer (IET) rates between the reduced heme [Fe(II)] and oxidized molybdenum [Mo(VI)] centers in the wild type, R160Q, and R160K human SO forms were investigated by laser flash photolysis. In the R160Q mutant, the IET rate constant at pH 6.0 was decreased by nearly 3 orders of magnitude relative to wild type, which indicates that the positive charge of Arg 160 is essential for efficient IET in human SO. Furthermore, the IET rate constant for the R160K mutant is about one-fourth that of the wild type enzyme, which strongly indicates that it is the loss of charge of Arg 160, and not its precise location, that is responsible for the much larger decrease in IET rates in the R160Q mutant. Steady-state kinetic measurements indicate that IET is rate-limiting in the catalytic cycle of the R160Q mutant. Thus, the large decrease in the IET rate constant rationalizes the fatal impact of this mutation in patients with this genetic disorder. 相似文献
692.
Hurley JB 《The Journal of general physiology》2002,119(2):125-128
693.
When a nascent vesicle buds, the membrane must curve. Several mechanisms have been proposed for curvature creation or stabilization. Structural analysis of the ENTH domain of the endocytic protein epsin has suggested a new mechanism, in which the ENTH domain pushes its way into membranes, thus bending them into shape. 相似文献
694.
Bode BP Fuchs BC Hurley BP Conroy JL Suetterlin JE Tanabe KK Rhoads DB Abcouwer SF Souba WW 《American journal of physiology. Gastrointestinal and liver physiology》2002,283(5):G1062-G1073
Human hepatoma cells take up glutamine at rates severalfold faster than the system N-mediated transport rates observed in normal human hepatocytes. Amino acid inhibition, kinetic, Northern blotting, RT-PCR, and restriction enzyme analyses collectively identified the transporter responsible in six human hepatoma cell lines as amino acid transporter B(0) (ATB(0)), the human ortholog of rodent ASCT2. The majority of glutamine uptake in liver fibroblasts and an immortalized human liver epithelial cell line (THLE-5B) was also mediated by ATB(0). The 2.9-kb ATB(0) mRNA was equally expressed in all cell lines, whereas expression of the system A transporters ATA2 and ATA3 was variable. In contrast, the system N isoforms (SN1 and SN2) were expressed only in well-differentiated hepatomas. ATB(0) mRNA was also expressed in cirrhotic liver and adult and pediatric liver cancer biopsies but was not detectable in isolated human hepatocytes or fetal liver. Although the growth of all hepatomas was glutamine dependent, competitive inhibition of ATB(0)-mediated glutamine uptake blocked proliferation only in poorly differentiated cells lacking SN1 or SN2 expression and exhibiting low glutamine synthetase mRNA levels. 相似文献
695.
Marchetti L Sabbieti MG Menghi M Materazzi S Hurley MM Menghi G 《Histology and histopathology》2002,17(4):1061-1066
We evaluated, by confocal laser scanning microscopy, the actin cytoskeleton of immortalized rat Py1a osteoblasts treated with phthalate esters (butyl benzyl phthalate, BBP and dibutyl phthalate, DBP), endocrine disruptors with estrogenic activity. We observed some peculiar modifications of actin cytoskeleton and cells changing from a spindle shape to a rounded form. In particular, F-actin formed thick bundles around the cell membrane but only a weak labeling was observed in rounded cells. Also influence on apoptosis and short-term effects on FGF-2 were studied. It was found that BBP and DBP exert their action in a similar way, act in a transient manner and do not induce apoptosis. 相似文献
696.
Burn JE Hurley UA Birch RJ Arioli T Cork A Williamson RE 《The Plant journal : for cell and molecular biology》2002,32(6):949-960
rsw3 is a temperature-sensitive mutant of Arabidopsis thaliana showing radially swollen roots and a deficiency in cellulose. The rsw3 gene was identified by a map-based strategy, and shows high similarity to the catalytic alpha-subunits of glucosidase II from mouse, yeast and potato. These enzymes process N-linked glycans in the ER, so that they bind and then release chaperones as part of the quality control pathway, ensuring correct protein folding. Putative beta-subunits for the glucosidase II holoenzyme identified in the Arabidopsis and rice genomes share characteristic motifs (including an HDEL ER-retention signal) with beta-subunits in mammals and yeast. The genes encoding the putative alpha- and beta-subunits are single copy and, like the rsw3 phenotype, widely expressed. rsw3 reduces cell number more strongly than cell size in stamen filaments and probably stems. Most features of the rsw3 phenotype are shared with other cellulose-deficient mutants, but some--notably, production of multiple rosettes and a lack of secreted seed mucilage--are not and may reflect glucosidase II affecting processes other than cellulose synthesis. The rsw3 root phenotype develops more slowly than the rsw1 and rsw2 phenotypes when seedlings are transferred to the restrictive temperature. This is consistent with rsw3 reducing glycoprotein delivery from the ER to the plasma membrane whereas rsw1 and rsw2 act more rapidly by affecting the properties of already delivered enzymes. 相似文献
697.
Mechanism of ubiquitin recognition by the CUE domain of Vps9p 总被引:9,自引:0,他引:9
Coupling of ubiquitin conjugation to ER degradation (CUE) domains are approximately 50 amino acid monoubiquitin binding motifs found in proteins of trafficking and ubiquitination pathways. The 2.3 A structure of the Vps9p-CUE domain is a dimeric domain-swapped variant of the ubiquitin binding UBA domain. The 1.7 A structure of the CUE:ubiquitin complex shows that one CUE dimer binds one ubiquitin molecule. The bound CUE dimer is kinked relative to the unbound CUE dimer and wraps around ubiquitin. The CUE monomer contains two ubiquitin binding surfaces on opposite faces of the molecule that cannot bind simultaneously to a single ubiquitin molecule. Dimerization of the CUE domain allows both surfaces to contact a single ubiquitin molecule, providing a mechanism for high-affinity binding to monoubiquitin. 相似文献
698.
Feng C Wilson HL Hurley JK Hazzard JT Tollin G Rajagopalan KV Enemark JH 《The Journal of biological chemistry》2003,278(5):2913-2920
Tyrosine 343 in human sulfite oxidase (SO) is conserved in all SOs sequenced to date. Intramolecular electron transfer (IET) rates between reduced heme (Fe(II)) and oxidized molybdenum (Mo(VI)) in the recombinant wild-type and Y343F human SO were measured for the first time by flash photolysis. The IET rate in wild-type human SO at pH 7.4 is about 37% of that in chicken SO with a similar decrease in k(cat). Steady-state kinetic analysis of the Y343F mutant showed an increase in K(m)(sulfite) and a decrease in k(cat) resulting in a 23-fold attenuation in the specificity constant k(cat)/K(m)(sulfite) at the optimum pH value of 8.25. This indicates that Tyr-343 is involved in the binding of the substrate and catalysis within the molybdenum active site. Furthermore, the IET rate constant in the mutant at pH 6.0 is only about one-tenth that of the wild-type enzyme, suggesting that the OH group of Tyr-343 is vital for efficient IET in SO. The pH dependences of IET rate constants in the wild-type and mutant SO are consistent with the previously proposed coupled electron-proton transfer mechanism. 相似文献
699.
700.
A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Markowitz M Louie M Hurley A Sun E Di Mascio M Perelson AS Ho DD 《Journal of virology》2003,77(8):5037-5038
Mathematical models provide an understanding of in vivo replication kinetics of human immunodeficiency virus type 1 (HIV-1). With a novel intervention designed for increased potency, we have more accurately deduced the half-lives of virus-producing CD4(+) T cells, 0.7 day, and the generation time of HIV-1 in vivo, approximately 2 days, confirming the dynamic nature of HIV-1 replication. 相似文献