全文获取类型
收费全文 | 522篇 |
免费 | 39篇 |
出版年
2022年 | 8篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 1篇 |
2016年 | 8篇 |
2015年 | 9篇 |
2014年 | 16篇 |
2013年 | 29篇 |
2012年 | 20篇 |
2011年 | 40篇 |
2010年 | 22篇 |
2009年 | 19篇 |
2008年 | 43篇 |
2007年 | 28篇 |
2006年 | 39篇 |
2005年 | 42篇 |
2004年 | 39篇 |
2003年 | 42篇 |
2002年 | 46篇 |
2001年 | 2篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 11篇 |
1994年 | 9篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1968年 | 3篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有561条查询结果,搜索用时 15 毫秒
121.
Koki Makabe Takashi Nakamura Debanjan Dhar Teikichi Ikura Shohei Koide Kunihiro Kuwajima 《Journal of molecular biology》2018,430(12):1799-1813
Although many naturally occurring proteins consist of multiple domains, most studies on protein folding to date deal with single-domain proteins or isolated domains of multi-domain proteins. Studies of multi-domain protein folding are required for further advancing our understanding of protein folding mechanisms. Borrelia outer surface protein A (OspA) is a β-rich two-domain protein, in which two globular domains are connected by a rigid and stable single-layer β-sheet. Thus, OspA is particularly suited as a model system for studying the interplays of domains in protein folding. Here, we studied the equilibria and kinetics of the urea-induced folding–unfolding reactions of OspA probed with tryptophan fluorescence and ultraviolet circular dichroism. Global analysis of the experimental data revealed compelling lines of evidence for accumulation of an on-pathway intermediate during kinetic refolding and for the identity between the kinetic intermediate and a previously described equilibrium unfolding intermediate. The results suggest that the intermediate has the fully native structure in the N-terminal domain and the single layer β-sheet, with the C-terminal domain still unfolded. The observation of the productive on-pathway folding intermediate clearly indicates substantial interactions between the two domains mediated by the single-layer β-sheet. We propose that a rigid and stable intervening region between two domains creates an overlap between two folding units and can energetically couple their folding reactions. 相似文献
122.
Isolation and characterization of cDNAs encoding vacuolar H+-pyrophosphatase isoforms from rice (Oryza sativa L.) 总被引:2,自引:0,他引:2
Yoshikiyo Sakakibara Hideyuki Kobayashi Kunihiro Kasamo 《Plant molecular biology》1996,31(5):1029-1038
The vacuolar H+-pyrophosphatase (V-PPase) is an electrogenic H+ pump, which was found in the plant vacuolar membrane. Two cDNA clones (OVP1 and OVP2) encoding the V-PPase were isolated from cultured rice (Oryza sativa L.) cells and subsequently sequenced. The sequence analysis has revealed thatOVP1 contains 2316 nucleotides of open reading frame (ORF) and 362 nucleotides of the 3-untranslated region, whereasOVP2 comprises 2304 nucleotides of ORF and 312 nucleotides of the 3-untranslated region. The nucleotide sequences of ORF ofOVP1 andOVP2 are 80.7% identical, and their 5- and 3-untranslated regions have 39.4% and 48.4% identity, respectively. The polypeptides encoded by the ORF ofOVP1 andOVP2 contain 771 and 767 amino acids, respectively, and the sequences of the OVP proteins are very similar to those of other V-PPases, which are shown to have 85–91% homology. Chromosomal mapping by RFLP techniques demonstrates that OVP1 and OVP2 are isoforms encoded by different genes. BothOVP1 andOVP2 are mapped on the same chromosome (chromosome 6) to a distance of ca. 90 cM. Northern analysis indicates that theOVP1 andOVP2 are also expressed in intact rice plants andOVP2 shows higher expression in the calli than the roots and shoots, compared toOVP1. These results show that at least two genes encoding the V-PPases are present in rice genome and their expressions are probably regulated in a different manner. 相似文献
123.
124.
An X-ray structural study of human ceruloplasmin in relation to ferroxidase activity 总被引:5,自引:0,他引:5
P. F. Lindley Graeme Card Irina Zaitseva Vjacheslav Zaitsev Bengt Reinhammar Eva Selin-Lindgren Kunihiro Yoshida 《Journal of biological inorganic chemistry》1997,2(4):454-463
The role of ceruloplasmin as a ferroxidase in the blood, mediating the release of iron from cells and its subsequent incorporation into serum transferrin, has long been the subject of speculation and debate. However, a recent X-ray crystal structure determination of human ceruloplasmin at a resolution of around 3.0?Å, in conjunction with studies associating mutations in the ceruloplasmin gene with systemic haemosiderosis in humans, has added considerable weight to the argument in favour of a ferroxidase role for this enzyme. Further X-ray studies have now been undertaken involving the binding of the cations Co(II), Fe(II), Fe(III), and Cu(II) to ceruloplasmin. These results give insights into a mechanism for ferroxidase activity in ceruloplasmin. The residues and sites involved in ferroxidation are similar to those proposed for the heavy chains of human ferritin. The nature of the ferroxidase activity of human ceruloplasmin is described in terms of its three-dimensional molecular structure. 相似文献
125.
126.
Samson O. Obado Marc Brillantes Kunihiro Uryu Wenzhu Zhang Natalia E. Ketaren Brian T. Chait Mark C. Field Michael P. Rout 《PLoS biology》2016,14(2)
The nuclear pore complex (NPC) is responsible for nucleocytoplasmic transport and constitutes a hub for control of gene expression. The components of NPCs from several eukaryotic lineages have been determined, but only the yeast and vertebrate NPCs have been extensively characterized at the quaternary level. Significantly, recent evidence indicates that compositional similarity does not necessarily correspond to homologous architecture between NPCs from different taxa. To address this, we describe the interactome of the trypanosome NPC, a representative, highly divergent eukaryote. We identify numerous new NPC components and report an exhaustive interactome, allowing assignment of trypanosome nucleoporins to discrete NPC substructures. Remarkably, despite retaining similar protein composition, there are exceptional architectural dissimilarities between opisthokont (yeast and vertebrates) and excavate (trypanosomes) NPCs. Whilst elements of the inner core are conserved, numerous peripheral structures are highly divergent, perhaps reflecting requirements to interface with divergent nuclear and cytoplasmic functions. Moreover, the trypanosome NPC has almost complete nucleocytoplasmic symmetry, in contrast to the opisthokont NPC; this may reflect divergence in RNA export processes at the NPC cytoplasmic face, as we find evidence supporting Ran-dependent mRNA export in trypanosomes, similar to protein transport. We propose a model of stepwise acquisition of nucleocytoplasmic mechanistic complexity and demonstrate that detailed dissection of macromolecular complexes provides fuller understanding of evolutionary processes. 相似文献
127.
Toshiyuki Nagai Yasuyuki Honda Yasuo Sugano Kunihiro Nishimura Michikazu Nakai Satoshi Honda Naotsugu Iwakami Atsushi Okada Yasuhide Asaumi Takeshi Aiba Teruo Noguchi Kengo Kusano Hisao Ogawa Satoshi Yasuda Toshihisa Anzai NaDEF investigators 《PloS one》2016,11(11)
BackgroundCirculating polyunsaturated fatty acid (PUFA) levels are associated with clinical outcomes in cardiovascular diseases including coronary artery disease and chronic heart failure (HF). However, their clinical implications in acute decompensated HF (ADHF) remain unclear. The aim of this study was to investigate the clinical roles of circulating PUFAs in patients with ADHF.MethodsCirculating levels of PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) and dihomo-gamma linoleic acid (DGLA), were measured on admission in 685 consecutive ADHF patients. Adverse events were defined as all-cause death and worsening HF.ResultsDuring a median follow-up period of 560 days, 262 (38.2%) patients had adverse events. Although patients with adverse events had lower n-6 PUFA (AA + DGLA) level than those without, n-3 PUFA (EPA + DHA) level was comparable between the groups. Kaplan-Meier analyses showed that lower n-6 PUFA level on admission was significantly associated with the composite of all-cause death and worsening HF, all-cause death, cardiovascular death and worsening HF (p < 0.001, p = 0.005, p = 0.021, p = 0.019, respectively). In a multivariate Cox model, lower n-6 PUFA level was independently associated with increased risk of adverse events (HR 0.996, 95% CI: 0.993–0.999, p = 0.027).ConclusionsLower n-6 but not n-3 PUFA level on admission was significantly related to worse clinical outcomes in ADHF patients. Measurement of circulating n-6 PUFA levels on admission might provide information for identifying high risk ADHF patients. 相似文献
128.
Subunits (, ß, ) and mixtures of subunits ( ß, , ß , ß ) were isolated without denaturationfrom a chloroform extract of chloroplast coupling factor 1 (CF1)from maize (Zea mays var. Ushiku 5-4) and from spinach by fastprotein liquid chromatography (FPLC), on an anion-exchange columnof Mono-Q in the presence of n-octylglucoside (OG) and on achromatofocusing column of Mono-P. The ß -subunitcomplex (CF1 ß ) was the minimum unit required forATPase activity, as was confirmed by the reconstituted complexof ß and subunits. An subunit isolated from maizeinhibited the ATPase activity of CF1 ß from bothmaize and spinach. CF1 ß was found to contain anOG-dependent Mg2+-ATPase. The ATPase activity of CF1 ß required divalent cations, such as Mg2+ or Mn2+, for its expressionin the presence of OG; its optimum pH was 8.0 and it was markedlyinhibited by NaN3. The enzyme hydrolyzed ATP in prefernece toGTP but not CTP, UTP, ADP, AMP or pNPP. Lineweaver-Burk plotsof its activity were curvilinear in the range of 0.60.7mM ATP.Mg2+.
1Present address: Department of Biology, School of Education,Waseda University, Shinjuku-ku, Tokyo, 160 Japan. (Received February 15, 1989; Accepted April 20, 1989) 相似文献
129.
Isao Saito Kazuyuki Hatakeyama Takahiro Kido Hiroaki Ohkubo Shigetada Nakanishi Kunihiro Ueda 《Gene》1990,90(2):249-254
The primary structure of bovine thymus poly(ADP-ribose) synthetase, as deduced from the nucleotide sequence of a cloned cDNA, indicated that this enzyme is composed of 1016 amino acids (aa) with an Mr of 113481. An abundance of Lys and Arg residues was in accord with the known basic nature of this protein. A comparison with reported sequences of human counterparts revealed: (1) three functional domains separated by partial proteolysis, i.e., DNA-binding (N-terminal), auto-modification (central), and NAD-binding (C-terminal) domains, have, in this order, increasing degrees of homology; (2) the DNA-binding domain is composed of two distinct regions: one, less conserved, containing zinc-binding fingers and the other, more conserved, containing helix-turn-helix motifs; (3) all Glu and Asp residues in the automodification domain are conserved; and (4) a 78-aa stretch encompassing the nucleotide-binding fold in the NAD-binding domain is completely conserved. These results are compatible with specific features of each domain, i.e., complex DNA-enzyme interactions, multiple automodification at acidic aa residues, and a stringent specificity for the substrate, NAD. 相似文献
130.
Mg++ -activated and -inhibited ATPases from mung bean hypocotyls 总被引:1,自引:0,他引:1
Mg++-activated and inhibited ATPases were isolated from dark-grownmung bean hypocotyls. The enzymes hydrolyzed nucleoside tri-,di- and monophosphates and ß-glycerophosphate. Theeffect of Mg++ was most marked when ATP and other nucleosidetriphosphates were used as substrates. Mg++-activated ATPases: The activity of enzyme-I was localizedin the membranes and was not released by treatment with 0.1%deoxycholate. Enzyme-II was released and separated by CM-cellulosecolumn chromatography. Enzyme-V was separated from the solublefraction of the cell homogenate by DEAE-cellulose column chromatography.The rates of activivation by Mg++ of enzyme-II and enzyme-Vwere very small compared to that of enzyme-I. Mg++-inhibited ATPases: Enzyme-II and -IV were precipitatedwith 5080% ammonium sulfate from the soluble fractionof the cell homogenate and were separated by successive columnchromatographies on Sepharose 6B and DEAE-cellulose. The activitiesof enzyme-III and -IV were inhibited by Mg++, when ATP, UTPand GTP were used as substrates. Enzyme-III was purified approximately38-fold, and was more remarkably inhibited by Mg++ than wasenzyme-IV.
1Present address: Institute for Plant Virus Research, 959 Aobacho,Chiba 280, Japan. (Received January 7, 1974; ) 相似文献