全文获取类型
收费全文 | 2344篇 |
免费 | 213篇 |
国内免费 | 2篇 |
专业分类
2559篇 |
出版年
2023年 | 7篇 |
2022年 | 15篇 |
2021年 | 30篇 |
2020年 | 24篇 |
2019年 | 18篇 |
2018年 | 41篇 |
2017年 | 34篇 |
2016年 | 59篇 |
2015年 | 107篇 |
2014年 | 129篇 |
2013年 | 132篇 |
2012年 | 175篇 |
2011年 | 157篇 |
2010年 | 105篇 |
2009年 | 104篇 |
2008年 | 143篇 |
2007年 | 154篇 |
2006年 | 177篇 |
2005年 | 146篇 |
2004年 | 121篇 |
2003年 | 124篇 |
2002年 | 138篇 |
2001年 | 29篇 |
2000年 | 20篇 |
1999年 | 24篇 |
1998年 | 35篇 |
1997年 | 22篇 |
1996年 | 30篇 |
1995年 | 24篇 |
1994年 | 32篇 |
1993年 | 18篇 |
1992年 | 28篇 |
1991年 | 15篇 |
1990年 | 13篇 |
1989年 | 19篇 |
1988年 | 12篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 13篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1978年 | 4篇 |
1976年 | 10篇 |
1975年 | 4篇 |
1972年 | 4篇 |
1971年 | 4篇 |
1965年 | 4篇 |
1951年 | 2篇 |
排序方式: 共有2559条查询结果,搜索用时 15 毫秒
91.
92.
Peroxiredoxins 总被引:7,自引:0,他引:7
Present knowledge on peroxiredoxins is reviewed with special emphasis on catalytic principles, specificities and biological function. Peroxiredoxins are low efficiency peroxidases using thiols as reductants. They appear to be fairly promiscuous with respect to the hydroperoxide substrate; the specificities for the donor substrate vary considerably between the subfamilies, comprising GSH, thioredoxin, tryparedoxin and the analogous CXXC motifs in bacterial AhpF proteins. Peroxiredoxins are definitely responsible for antioxidant defense in bacteria (AhpC), yeast (thioredoxin peroxidase) and trypanosomatids (tryparedoxin peroxidase). They are considered to determine virulence of mycobacteria and trypanosomatids. In higher plants they are involved in balancing hydroperoxide production during photosynthesis. In higher animals peroxiredoxins appear to be involved in the redox-regulation of cellular signaling and differentiation, displaying in part opposite effects. 相似文献
93.
While helical transmembrane (TM) region prediction tools achieve high (>90%) success rates for real integral membrane proteins, they produce a considerable number of false positive hits in sequences of known nontransmembrane queries. We propose a modification of the dense alignment surface (DAS) method that achieves a substantial decrease in the false positive error rate. Essentially, a sequence that includes possible transmembrane regions is compared in a second step with TM segments in a sequence library of documented transmembrane proteins. If the performance of the query sequence against the library of documented TM segment-containing sequences in this test is lower than an empirical threshold, it is classified as a non-transmembrane protein. The probability of false positive prediction for trusted TM region hits is expressed in terms of E-values. The modified DAS method, the DAS-TMfilter algorithm, has an unchanged high sensitivity for TM segments ( approximately 95% detected in a learning set of 128 documented transmembrane proteins). At the same time, the selectivity measured over a non-redundant set of 526 soluble proteins with known 3D structure is approximately 99%, mainly because a large number of falsely predicted single membrane-pass proteins are eliminated by the DAS-TMfilter algorithm. 相似文献
94.
Fliih, a gelsolin-related cytoskeletal regulator essential for early mammalian embryonic development 下载免费PDF全文
Campbell HD Fountain S McLennan IS Berven LA Crouch MF Davy DA Hooper JA Waterford K Chen KS Lupski JR Ledermann B Young IG Matthaei KI 《Molecular and cellular biology》2002,22(10):3518-3526
The Drosophila melanogaster flightless I gene is required for normal cellularization of the syncytial blastoderm. Highly conserved homologues of flightless I are present in Caenorhabditis elegans, mouse, and human. We have disrupted the mouse homologue Fliih by homologous recombination in embryonic stem cells. Heterozygous Fliih mutant mice develop normally, although the level of Fliih protein is reduced. Cultured homozygous Fliih mutant blastocysts hatch, attach, and form an outgrowing trophoblast cell layer, but egg cylinder formation fails and the embryos degenerate. Similarly, Fliih mutant embryos initiate implantation in vivo but then rapidly degenerate. We have constructed a transgenic mouse carrying the complete human FLII gene and shown that the FLII transgene is capable of rescuing the embryonic lethality of the homozygous targeted Fliih mutation. These results confirm the specific inactivation of the Fliih gene and establish that the human FLII gene and its gene product are functional in the mouse. The Fliih mouse mutant phenotype is much more severe than in the case of the related gelsolin family members gelsolin, villin, and CapG, where the homozygous mutant mice are viable and fertile but display alterations in cytoskeletal actin regulation. 相似文献
95.
Tryparedoxin peroxidases (TXNPx) catalyze hydroperoxide reduction by tryparedoxin (TXN) by an enzyme substitution mechanism presumed to involve three catalytic intermediates: (i) a transient oxidation state having C52 oxidized to a sulfenic acid, (ii) the stable oxidized form with C52 disulfide-bound to C173', and (iii) a semi-reduced intermediate with C40 of TXN disulfide-linked to C173' from which the ground state enzyme is regenerated by thiol/disulfide reshuffling. This kinetically unstable form was mimmicked by a dead-end intermediate generated by cooxidation of TXNPx of Trypanosoma brucei brucei with an inhibitory mutein of TXN in which C43 was replaced by serine (TbTXNC43S). Cleavage of the isolated dead-end intermediate by trypsin plus chymotrypsin yielded a fragment that complied in size with the TbTXNC43S sequence 36 to 44 disulfide-linked to the TbTXNPx sequence 169 to 177. The presumed nature of the proteolytic fragment was confirmed by MS/MS sequencing. The results provide direct chemical evidence for the assumption that the reductive part of the catalysis is initiated by an attack of the substrate's solvent-exposed C40 on C173' of the oxidized peroxidase and, thus, confirm the hypothesis on the interaction of 2-Cys-peroxiredoxins with their proteinaceous substrates. 相似文献
96.
97.
Chen YT Alpen B Ono T Gure AO Scanlan MA Biggs WH Arden K Nakayama E Old LJ 《Genomics》2003,82(6):628-636
Human SSX was first identified as the gene involved in the t(X;18) translocation in synovial sarcoma. SSX is a multigene family, with 9 complete genes on chromosome Xp11. Normally expressed almost exclusively in testis, SSX mRNA is expressed in various human tumors, defining SSX as a cancer/testis antigen. We have now cloned the mouse ortholog of SSX. Mouse SSX genes can be divided into Ssxa and Ssxb subfamilies based on sequence homology. Ssxa has only one member, whereas 12 Ssxb genes, Ssxb1 to Ssxb12, were identified by cDNA cloning from mouse testis and mouse tumors. Both Ssxa and Ssxb are located on chromosome X and show tissue-restricted mRNA expression to testis among normal tissues. All putative human and mouse SSX proteins share conserved KRAB and SSX-RD domains. Mouse tumors were found to express some, but not all, Ssxb genes, similar to the SSX activation in human tumors. 相似文献
98.
Parolini O Weinhäusel A Kagerbauer B Sassmann J Holter W Gadner H Haas OA Knapp W 《Immunogenetics》2003,55(2):116-121
99.
Emmrich M Floss H Zühlsdorf B Martiny H 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,795(2):363-370
Glutardialdehyde (GDA) is the most commonly used disinfectant for flexible endoscopes. After inappropriate rinsing of endoscopes residual GDA in the narrow endoscope channels may lead to toxic effects in patients. Common methods for determination of aldehydes in water involve derivatization with 2,4-dinitrophenylhydrazine (DNPH), liquid-liquid or solid-phase extraction and HPLC determination. Since derivatization and extraction is both time-consuming and labor-intensive only a small number of samples can be measured. Thus, we developed a fully automated method which includes a conventional HPLC system, a programmable autosampler, and UV detection. After GDA derivatization using DNPH the samples remain in the aqueous phase and no preconcentration of the analyte is necessary. The samples are automatically derivatized through the autosampler. While derivatization in one sample takes place the previous sample is injected and measured by HPLC. Our method is well suited for screening residual GDA in endoscopes as it is both time- and labor-saving. 相似文献
100.
RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain 总被引:21,自引:0,他引:21
Deane R Du Yan S Submamaryan RK LaRue B Jovanovic S Hogg E Welch D Manness L Lin C Yu J Zhu H Ghiso J Frangione B Stern A Schmidt AM Armstrong DL Arnold B Liliensiek B Nawroth P Hofman F Kindy M Stern D Zlokovic B 《Nature medicine》2003,9(7):907-913
Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Abeta in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis. 相似文献