全文获取类型
收费全文 | 591篇 |
免费 | 49篇 |
专业分类
640篇 |
出版年
2021年 | 3篇 |
2019年 | 5篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 11篇 |
2015年 | 16篇 |
2014年 | 17篇 |
2013年 | 33篇 |
2012年 | 21篇 |
2011年 | 30篇 |
2010年 | 14篇 |
2009年 | 20篇 |
2008年 | 29篇 |
2007年 | 32篇 |
2006年 | 33篇 |
2005年 | 26篇 |
2004年 | 24篇 |
2003年 | 24篇 |
2002年 | 26篇 |
2001年 | 24篇 |
2000年 | 23篇 |
1999年 | 20篇 |
1998年 | 8篇 |
1997年 | 10篇 |
1996年 | 8篇 |
1995年 | 2篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 13篇 |
1991年 | 12篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 14篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 13篇 |
1984年 | 9篇 |
1983年 | 9篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有640条查询结果,搜索用时 0 毫秒
91.
Matsuo Y Morimoto T Kuwano M Loh PC Oshima T Ogasawara N 《The Journal of biological chemistry》2006,281(12):8110-8117
Bacillus subtilis YlqF belongs to the Era/Obg subfamily of small GTP-binding proteins and is essential for bacterial growth. Here we report that YlqF participates in the late step of 50 S ribosomal subunit assembly. YlqF was co-fractionated with the 50 S subunit, depending on the presence of noncleavable GTP analog. Moreover, the GTPase activity of YlqF was stimulated specifically by the 50 S subunit in vitro. Dimethyl sulfate footprinting analysis disclosed that YlqF binds to a unique position in 23 S rRNA. Yeast two-hybrid data revealed interactions between YlqF and the B. subtilis L25 protein (Ctc). The interaction was confirmed by the pull-down assay of the purified proteins. Specifically, YlqF is positioned around the A-site and P-site on the 50 S subunit. Proteome analysis of the abnormal 50 S subunits that accumulated in YlqF-depleted cells showed that L16 and L27 proteins, located near the YlqF-binding domain, are missing. Our results collectively indicate that YlqF will organize the late step of 50 S ribosomal subunit assembly. 相似文献
92.
Neuritic plaques are the key pathological feature of Alzheimer's disease, and amyloid beta (Abeta) peptides are major component of these plaques. In this study, we demonstrated the influence of aluminum (Al) on the Abeta peptide degradation by cathepsin D. Al did not directly affect the cathepsin D activity using small synthetic substrate. However, when Abeta peptides were used as substrate, the apparent inhibitory effect of Al on cathepsin D activity was observed. This inhibitory effect disappeared by treatment of desferrioxamine. These results indicate that Al has the potential to interact and disrupt Abeta peptide catabolism via the inhibition of proteolytic degradation. 相似文献
93.
Ogasawara Y Ohminato T Nakamura Y Ishii K 《The international journal of biochemistry & cell biology》2012,44(7):1072-1077
Peroxiredoxin 2, a typical 2-Cys peroxiredoxin, is the third most abundant protein in erythrocytes. It is understood that the physiologically functional state of peroxiredoxin 2 is the monomer, and that its role in scavenging low levels of H(2)O(2) results in the formation of disulfide-linked dimers, which are reversibly reduced to monomers by the thioredoxin-thioredoxin reductase system. Additionally, peroxiredoxins are highly susceptible to sulfinic acid formation through reactions with various peroxides. This overoxidized form, which is thought to convert peroxiredoxins into molecular chaperones and to be accompanied by a transition to polymeric forms, can be reversed by sulfiredoxins. However, physiological conformational changes and the antioxidant role of erythrocyte peroxiredoxin 2 are still unclear because there is low sulfiredoxin and thioredoxin-thioredoxin reductase activity in erythrocytes. In this study, we examined the structural and redox states of peroxiredoxin 2 in fresh hemolysates and estimated the activities of native and overoxidized peroxiredoxin 2 purified from red blood cells to clear the physiological roles of peroxiredoxin 2 in erythrocyte. Our findings demonstrate that native peroxiredoxin 2 exists as high molecular weight (>160 kDa) oligomers and that decamers or higher order molecular weight oligomers (260-460 kDa) have peroxidase activity. We further showed that peroxiredoxin 2 oligomers, which were predominantly composed of monomers in the reduced form, exert a chaperone activity equal to that of overoxidized peroxiredoxin 2 polymers. These results provide the novel insight that redox-active peroxiredoxin 2 functions in human red blood cells as high molecular weight oligomers that possess peroxidase and chaperone activities. 相似文献
94.
Tetsushi Kawai Hikaru Nakazawa Noriko Ida Hirofumi Okada Shuji Tani Jun-ichi Sumitani Takashi Kawaguchi Wataru Ogasawara Yasushi Morikawa Yoshinori Kobayashi 《Journal of industrial microbiology & biotechnology》2012,39(12):1741-1749
Although the capabilities of Trichoderma reesei cellulases have been greatly improved, these enzymes are still too costly for commercial use. The aim of this research was to assess the biomass saccharification capability of JN11, a recombinant cellulase, compared with that of the commercially available cellulases Accellerase 1500 and Cellic CTec. The activities of JN11, Accellerase 1500, and Cellic CTec were compared by using various types of cellulosic biomass, including rice straw, Erianthus, eucalyptus, and Japanese cedar. JN11 had higher saccharification capability for rice straw, Erianthus, eucalyptus, and Japanese cedar compared with the commercial cellulases. The JN11 saccharification of cellulosic biomasses, including hemicellulose (NaOH-pretreated biomasses), resulted in high glucose and xylose yields because of the high xylanase/xylosidase activity of JN11. Moreover, even JN11 saccharification of hemicellulose-free biomasses (sulfuric acid-, hydrothermally, and steam exploded-pretreated biomasses) resulted in high glucose yields. The cellulase activity of JN11, however, was comparable to that of its commercial counterparts. These findings indicate that the saccharification ability of cellulase is unrelated to its cellulase activity when measured against Avicel, CMC, pNP-lactoside, and other substrates. JN11 showed high activity for all types of pretreated cellulosic biomasses, indicating its usefulness for saccharification of various cellulosic biomasses. 相似文献
95.
96.
Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor 总被引:1,自引:0,他引:1
Harayama T Shindou H Ogasawara R Suwabe A Shimizu T 《The Journal of biological chemistry》2008,283(17):11097-11106
Platelet-activating factor (PAF) is a potent lipid mediator playing various inflammatory and physiological roles. PAF is biosynthesized through two independent pathways called the de novo and remodeling pathways. Lyso-PAF acetyltransferase (lyso-PAF AT) was believed to biosynthesize PAF under inflammatory conditions, through the remodeling pathway. The first isolated lyso-PAF AT (LysoPAFAT/LPCAT2) had consistent properties. However, we show in this study the finding of a second lyso-PAF AT working under noninflammatory conditions. We partially purified a Ca(2+)-independent lyso-PAF AT from mouse lung. Immunoreactivity for lysophosphatidylcholine acyltransferase 1 (LPCAT1) was detected in the active fraction. Lpcat1-transfected Chinese hamster ovary cells exhibited both LPCAT and lyso-PAF AT activities. We confirmed that LPCAT1 transfers acetate from acetyl-CoA to lyso-PAF by the identification of an acetyl-CoA (and other acyl-CoAs) interacting site in LPCAT1. We further showed that LPCAT1 activity and expression are independent of inflammatory signals. Therefore, these results suggest the molecular diversity of lyso-PAF ATs is as follows: one (LysoPAFAT/LPCAT2) is inducible and activated by inflammatory stimulation, and the other (LPCAT1) is constitutively expressed. Each lyso-PAF AT biosynthesizes inflammatory and physiological amounts of PAF, depending on the cell type. These findings provide important knowledge for the understanding of the diverse pathological and physiological roles of PAF. 相似文献
97.
The vasopressin (VP)/oxytocin (OT) superfamily peptides are one of the most widely distributed neuropeptides and/or neurohypophysial hormones, but have ever not been characterized from any deuterostome invertebrates including protochordates, ascidians. In the present study, we show the identification of a novel VP/OT superfamily peptide and its receptor in the ascidian, Ciona intestinalis. Intriguingly, the Ciona VP/OT-related peptide (Ci-VP), unlike other 9-amino acid and C-terminally amidated VP/OT superfamily peptides, consists of 13 amino acids and lacks a C-terminal amidation. Mass spectrometry confirmed the presence of the 13-residue Ci-VP in the neural complex. Furthermore, 10 of 14 cysteines are conserved in the neurophysin domain, compared with other VP/OT counterparts. These results revealed that the VP/OT superfamily is conserved in ascidians, but the Ci-VP gene encodes an unprecedented VP/OT-related peptide and neurophysin protein. Ci-VP was also shown to activate its endogenous receptor, Ci-VP-R, at physiological concentrations, confirming the functionality of Ci-VP as an endogenous ligand. The Ci-VP gene was expressed exclusively in neurons of the brain, whereas the Ci-TK-R mRNA was distributed in various tissues including the neural complex, alimentary tract, gonad, and heart. These expression profiles suggest that Ci-VP, like other VP/OT superfamily peptides, serves as a multifunctional neuropeptides. Altogether, our data revealed both evolutionary conservation and specific divergence of the VP/OT superfamily in protochordates. This is the first molecular characterization of a VP/OT superfamily peptide and its cognate receptor from not only ascidians but also deuterostome invertebrates. 相似文献
98.
Hayatsu N Ogasawara S Kaneko MK Kato Y Narimatsu H 《Biochemical and biophysical research communications》2008,368(2):217-222
Keratan sulfate (KS) proteoglycan is expressed in the extracellular matrix or cell surface in numerous tissues, predominantly in those of the cornea, cartilage, and brain. However, its structure, function, and regulation remain poorly understood. Our investigation of KS expression in glioblastoma cell lines using Western-blot and flow cytometry with anti-KS antibody (5D4) revealed that LN229 glioblastoma cell highly expresses KS on a cell surface. Real-time PCR analysis showed that LN229 expresses a high level of keratan sulfate Gal-6-sulfotransferase. Results of this study also demonstrate that recombinant 5D4-reactive aggrecan is produced in LN229. Taken together, these results suggest that LN229 produces 5D4-reactive highly sulfated KS and is useful to investigate the KS structure and function in glioblastoma. 相似文献
99.
Activation of the phagocyte NADPH oxidase, a superoxide-generating enzyme, involves assembly of cytosolic p47(phox), p67(phox), and rac with the membrane-associated cytochrome b(558). Following cell-free activation, enzymatic activity is highly labile [Tamura, M., Takeshita, M., Curnutte, J. T., Uhlinger, D. J., and Lambeth, J. D. (1992) J. Biol. Chem. 267, 7529-7538]. In an attempt to stabilize the activity and to investigate the nature of the complex, we have produced fusion proteins between rac and a C-terminal truncated form of p67(phox) (residues 1-210, 67N), which is a minimal active fragment. In a cell-free system, a fusion protein 67N-rac had higher activity and a 3-fold higher affinity than the individual cytosolic proteins, and 67N-Ser3-rac, which has a longer linker, showed a similar activity with the individual proteins. In contrast, rac-67N, a fusion in the opposite orientation, showed considerably lower activity. The enzyme activity reconstituted with 67N-rac showed a 10-fold higher stability and a lower K(m) for NADPH than the individual components. In the absence of p47, 67N-rac fusion protein at a high concentration showed nearly full activation, which was higher than that with the individual components. These results indicate that covalent binding between p67N and rac in the correct order produces a more stable complex than the individual components, suggesting that interactions among the subunits significantly influence the duration of the oxidase activation. On the basis of these findings, we propose a model for the topology among rac, 67N, and cytochrome b(558). 相似文献
100.