全文获取类型
收费全文 | 514篇 |
免费 | 32篇 |
出版年
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 10篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 11篇 |
2014年 | 7篇 |
2013年 | 85篇 |
2012年 | 33篇 |
2011年 | 25篇 |
2010年 | 24篇 |
2009年 | 15篇 |
2008年 | 26篇 |
2007年 | 28篇 |
2006年 | 28篇 |
2005年 | 30篇 |
2004年 | 40篇 |
2003年 | 33篇 |
2002年 | 33篇 |
2001年 | 6篇 |
2000年 | 10篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1977年 | 3篇 |
1975年 | 4篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1967年 | 2篇 |
1963年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有546条查询结果,搜索用时 31 毫秒
81.
The hypocholesterolemic effect of taurine was examined in mice fed a high-cholesterol diet containing 1% cholesterol and 0.25% sodium cholate. Male C57BL/6 mice were divided into 3 groups: control group (HC), 1% taurine-supplemented group (HCT+), and taurine-deficient group (HCT-) produced by supplying 0.5% guanidinoethyl sulfonate (GES) solution ad libitum instead of water. After they were fed with the respective diet or drinking water for 4 weeks, the liver taurine level was reduced 80% in the HCT- group compared with that in the HC group, although there was no difference in the serum taurine amount between the two groups. The formation ratio of cholesterol gallstones increased from 71% to 100% by taurine deficiency, and decreased to 0% by taurine supplementation. Compared with the HC group, serum and liver cholesterol significantly decreased, and the excretion of fecal bile acid notably rose in the HCT+ group but tended to lower in the HCT- group. There were no differences in LDL receptor protein level among the three groups. In the subsequent experiment, triglycerides (TG) secretion rate was determined and found to be significantly suppressed by taurine supplementation. In conclusion, it is suggested that taurine does not up-regulate LDL receptor protein level, and the decrease in cholesterol in the circulation is mainly due to its suppressive effect on TG secretion from the liver. 相似文献
82.
Timothy Reed Gerald H. Lushington Yan Xia Hidehiko Hirakawa DeAnna M. Travis Minae Mure Emily E. Scott Julian Limburg 《The Journal of biological chemistry》2010,285(33):25782-25791
Histamine dehydrogenase (HADH) isolated from Nocardioides simplex catalyzes the oxidative deamination of histamine to imidazole acetaldehyde. HADH is highly specific for histamine, and we are interested in understanding the recognition mode of histamine in its active site. We describe the first crystal structure of a recombinant form of HADH (HADH) to 2.7-Å resolution. HADH is a homodimer, where each 76-kDa subunit contains an iron-sulfur cluster ([4Fe-4S]2+) and a 6-S-cysteinyl flavin mononucleotide (6-S-Cys-FMN) as redox cofactors. The overall structure of HADH is very similar to that of trimethylamine dehydrogenase (TMADH) from Methylotrophus methylophilus (bacterium W3A1). However, some distinct differences between the structure of HADH and TMADH have been found. Tyr60, Trp264, and Trp355 provide the framework for the “aromatic bowl” that serves as a trimethylamine-binding site in TMADH is comprised of Gln65, Trp267, and Asp358, respectively, in HADH. The surface Tyr442 that is essential in transferring electrons to electron-transfer flavoprotein (ETF) in TMADH is not conserved in HADH. We use this structure to propose the binding mode for histamine in the active site of HADH through molecular modeling and to compare the interactions to those observed for other histamine-binding proteins whose structures are known. 相似文献
83.
84.
Identification of amino acid residues essential for heparin binding by the A1 domain of human von Willebrand factor 总被引:1,自引:0,他引:1
Adachi T Matsushita T Dong Z Katsumi A Nakayama T Kojima T Saito H Sadler JE Naoe T 《Biochemical and biophysical research communications》2006,339(4):1178-1183
Platelet adhesion is mediated by von Willebrand factor (VWF) that binds platelet glycoprotein Ib (GPIb). Previous observations suggested that heparin competitively inhibits the binding of VWF to GPIb and may down-regulate platelet adhesion. We performed charged-to-alanine scanning mutagenesis of domain A1 and studied dose-dependent binding to heparin-Sepharose beads. Mutations at Lys1362 and Arg1395, at which the GPIb binding was markedly decreased, showed 41% and 42% binding, respectively. Clustered mutations in the segments 1332KDRKR1336 and 1405KKKK1408, which have been proposed as heparin binding sequences, showed 72% and 52% binding, respectively. However, single alanine substitutions within these clusters showed normal binding. Our findings suggest that heparin may inhibit the binding of VWF to GPIb by interacting with GPIb binding and interpret why some hemorrhagic complications of heparin therapy are not predictable based on techniques for monitoring the conventional anticoagulant effects of heparin. 相似文献
85.
Yuji Masuda Miki Suzuki Hidehiko Kawai Asami Hishiki Hiroshi Hashimoto Chikahide Masutani Takashi Hishida Fumio Suzuki Kenji Kamiya 《Nucleic acids research》2012,40(20):10394-10407
Post-replication DNA repair in eukaryotes is regulated by ubiquitination of proliferating cell nuclear antigen (PCNA). Monoubiquitination catalyzed by RAD6–RAD18 (an E2–E3 complex) stimulates translesion DNA synthesis, whereas polyubiquitination, promoted by additional factors such as MMS2–UBC13 (a UEV–E2 complex) and HLTF (an E3 ligase), leads to template switching in humans. Here, using an in vitro ubiquitination reaction system reconstituted with purified human proteins, we demonstrated that PCNA is polyubiquitinated predominantly via en bloc transfer of a pre-formed ubiquitin (Ub) chain rather than by extension of the Ub chain on monoubiquitinated PCNA. Our results support a model in which HLTF forms a thiol-linked Ub chain on UBC13 (UBC13∼Ubn) and then transfers the chain to RAD6∼Ub, forming RAD6∼Ubn+1. The resultant Ub chain is subsequently transferred to PCNA by RAD18. Thus, template switching may be promoted under certain circumstances in which both RAD18 and HLTF are coordinately recruited to sites of stalled replication. 相似文献
86.
87.
Hidehiko Hirakawa Suguru Ishikawa Teruyuki Nagamune 《Biotechnology and bioengineering》2012,109(12):2955-2961
The catalytic activity of Staphylococcus aureus sortase A (SaSrtA) is dependent on Ca2+, because binding of Ca2+ to Glu residues distal to the active site stabilizes the substrate binding site. To obtain Ca2+‐independent SaSrtA, we substituted two Glu residues in the Ca2+‐binding pocket (Glu105 and Glu108). Although single mutations decreased SaSrtA activity, mutations of both Glu105 and Glu108 resulted in Ca2+‐independent activity. Kinetic analysis suggested that the double mutations affect the substrate binding site, without affecting substrate specificity. This approach will allow us to develop SaSrtA variants suitable for various applications, including in vivo site‐specific protein modification and labeling. Biotechnol. Bioeng. 2012; 109: 2955–2961. © 2012 Wiley Periodicals, Inc. 相似文献
88.
Unique Induction of CA1 LTP Components After Intake of Theanine, an Amino Acid in Tea Leaves and its Effect on Stress Response 总被引:1,自引:0,他引:1
Takeda A Tamano H Suzuki M Sakamoto K Oku N Yokogoshi H 《Cellular and molecular neurobiology》2012,32(1):41-48
Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. This study was undertaken to evaluate
the effect of theanine intake on long-term potentiation (LTP) induction at hippocampal CA1 synapses and exposure to acute
stress. Young rats were fed water containing 0.3% theanine after birth. Key findings: Serum corticosterone level was markedly
decreased by theanine intake. Because this decrease can modify synaptic plasticity, the effect of theanine intake was examined
focused on CA1 LTP induction. CA1 LTP induced by a 100-Hz tetanus for 1 s was almost the same extent in hippocampal slices
from theanine-administered rats, whereas that induced by a 200-Hz tetanus for 1 s was significantly attenuated. 2-Amino-5-phosphonovalerate
(APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, significantly attenuated CA1 LTP induced by a 200-Hz tetanus in the control rats, but
not in theanine-administered rats. Interestingly, APV completely blocked CA1 LTP induced by a 100-Hz tetanus in the control
rats, while scarcely blocking it in theanine-administered rats. These results indicate that theanine intake reduces NMDA receptor-dependent
CA1 LTP, while increasing NMDA receptor-independent CA1 LTP. Furthermore, neither 100-Hz tetanus-induced LTP nor 200-Hz tetanus-induced
LTP was attenuated in theanine-administered rats after exposure to tail suspension stress, suggesting that the lack of NMDA
receptor-dependent CA1 LTP by theanine intake is involved in ameliorating the attenuation of CA1 LTP after tail suspension.
This study is the first to indicate that theanine intake modifies the mechanism of CA1 LTP induction. 相似文献
89.
90.
Hideyuki Suzuki Nobukazu Miyakawa Hidehiko Kumagai 《Enzyme and microbial technology》2002,30(7):883-888
γ-L-Glutamyltaurine is a naturally occurring peptide and known to have several physiological functions in mammals. This paper describes a new method for the enzymatic production of γ-L-glutamyltaurine from L-glutamine and taurine through the transpeptidation reaction of γ-glutamyltranspeptidase (EC 2.3.2.2) of Escherichia coli K-12. The optimum conditions for the production of γ-L-glutamyltaurine were 200 mM L-glutamine, 200 mM taurine and 0.2 U/ml γ-glutamyltranspeptidase, pH 10, and 1-h incubation at 37°C. Forty-five mM γ-L-glutamyltaurine was obtained, the yield being 22.5%. γ-L-Glutamyltaurine was purified on Dowex 1 × 8 and C18 columns, and identified by means of NMR and a polarimeter. 相似文献