全文获取类型
收费全文 | 2147篇 |
免费 | 134篇 |
出版年
2024年 | 5篇 |
2023年 | 19篇 |
2022年 | 31篇 |
2021年 | 57篇 |
2020年 | 29篇 |
2019年 | 43篇 |
2018年 | 61篇 |
2017年 | 49篇 |
2016年 | 65篇 |
2015年 | 101篇 |
2014年 | 99篇 |
2013年 | 151篇 |
2012年 | 182篇 |
2011年 | 155篇 |
2010年 | 110篇 |
2009年 | 95篇 |
2008年 | 146篇 |
2007年 | 130篇 |
2006年 | 114篇 |
2005年 | 119篇 |
2004年 | 83篇 |
2003年 | 73篇 |
2002年 | 82篇 |
2001年 | 28篇 |
2000年 | 23篇 |
1999年 | 18篇 |
1998年 | 31篇 |
1997年 | 14篇 |
1996年 | 13篇 |
1995年 | 14篇 |
1994年 | 8篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 12篇 |
1990年 | 9篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1969年 | 1篇 |
排序方式: 共有2281条查询结果,搜索用时 125 毫秒
921.
M. V. R. Rao M. Atreyi G. Suresh Kumar Satish Kumar V. S. Chauhan 《Journal of biosciences》1985,8(3-4):635-644
The interaction of the oligopeptides Ala-Gln-GIn-Leu-Ala-Gly-OH and Gln-Leu-Ala-Gly-OMe corresponding, respectively, to the
sequence 53–58 and 55–58 oflac repressor protein with four polynucleotides was studied. The two peptides did not interact with poly dA. poly dT, poly d(A-T)·poly
d(A-T) or poly d(A-G)·poly d(C-T). But they interacted in a characteristic way with poly d(A-C). poly d (G-T), the sequences
of which are in abundance in thelac operator region. Both the peptides stabilised the melting of poly d (A-C). poly d (G-T) at a peptide to nucleotide ratio
(P/N) of 4; at lower ratios, they destabilised the DNA slightly. The circular dichroism of the alternating polynucleotide
with CAC/GTG sequences was perturbed by both the oligopeptides. The hexapeptide at a P/N of 4 caused the transformation of
the B-form circular dichroism spectrum to a new state, characterised by strong 220 and 240 nm bands, and a rather weak long
wavelength spectrum. 相似文献
922.
Carina M. Henningsson Subnaicker Selvaraj Grant D. MacLean Mavanur R. Suresh Antoine A. Noujaim B. Michael Longenecker 《Cancer immunology, immunotherapy : CII》1987,25(3):231-241
Summary The Thomsen, Friedenreich (TF) and Tn carbohydrate antigens are expressed on the vast majority of human adenocarcinomas and are associated with aggressive behavior of certain tumors. TF and Tn antigens are also expressed on certain murine cancer cell lines including TA3-Ha, a highly lethal, transplantable mammary adenocarcinoma. TF and Tn cancer-associated carbohydrate haptens were synthesized, conjugated to protein carriers and used to demonstrate that delayed-type hypersensitivity (DTH) effector T cells can specifically recognize and respond to carbohydrate determinants on the TA3-Ha tumor-associated glycoprotein, epiglycanin. The effector cells were shown to have the helper DTH phenotype (Lytl+, Lyt2–, Thyl+) and it was demonstrated that they respond to specific carbohydrate determinants in an MHC-restricted fashion. These experiments provide the rationale for the use of synthetic tumor-associated glycoconjugates (S-TAGs) to stimulate anticancer T cell immunity. In support of this hypothesis, it was shown that preimmunization with the appropriate S-TAGs could provide a degree of protection against a subsequent tumor transplant and that antitumor effector Lytl+, Lyt2– T cells could be generated in vitro using the appropriate S-TAGs as antigens. 相似文献
923.
924.
The functionally conserved nucleoporins Nup124p from fission yeast and the human Nup153 mediate nuclear import and activity of the Tf1 retrotransposon and HIV-1 Vpr 下载免费PDF全文
Varadarajan P Mahalingam S Liu P Ng SB Gandotra S Dorairajoo DS Balasundaram D 《Molecular biology of the cell》2005,16(4):1823-1838
We report that the fission yeast nucleoporin Nup124p is required for the nuclear import of both, retrotransposon Tf1-Gag as well as the retroviral HIV-1 Vpr. Failure to import Tf1-Gag into the nucleus in a nup124 null mutant resulted in complete loss of Tf1 transposition. Similarly, nuclear import of HIV-1 Vpr was impaired in nup124 null mutant strains and cells became resistant to Vpr's cell-killing activity. On the basis of protein domain similarity, the human nucleoporin Nup153 was identified as a putative homolog of Nup124p. We demonstrate that in vitro-translated Nup124p and Nup153 coimmunoprecipitate Tf1-Gag or HIV-1 Vpr. Though full-length Nup153 was unable to complement the Tf1 transposition defect in a nup124 null mutant, we provide evidence that both nucleoporins share a unique N-terminal domain, Nup124p(AA264-454) and Nup153(AA448-634) that is absolutely essential for Tf1 transposition. Epigenetic overexpression of this domain in a wild-type (nup124(+)) background blocked Tf1 activity implying that sequences from Nup124p and the human Nup153 challenged the same pathway affecting Tf1 transposition. Our results establish a unique relationship between two analogous nucleoporins Nup124p and Nup153 wherein the function of a common domain in retrotransposition is conserved. 相似文献
925.
The compounds [Cu(dien)(2-PhIm)(ClO4)](ClO4) (1); [Cu(dien)(2-MeBzIm)](ClO4)2 (2); where dien = diethylenetriamine, 2-PhIm = 2-phenylimidazole and 2-MeBzIm = 2-methylbenzimidazole, were synthesized and characterized. The complexes possessing [Cu(II)dien] moiety as common, the former containing 2-phenylimidazole, yielded square pyramidal geometry with apical perchlorate coordination [Cu1-O(5) = 2.449 Å], while the latter with 2-methylbenzimidazole formed square planar geometry with weak perchlorate contact [Cu1-O(8) = 2.596 Å] in its apical position. The effect of solvent and the variable temperature 1H NMR investigation combinedly explore the geometrical rearrangement towards five coordination around Cu(II) metal center by accommodating the solvent molecule in its fifth coordination. Possessing easily labile perchlorate anion, both these complexes were investigated for their oxidation capability using 3,5-di-tert-butyl catechol (DTBC). The rate constant determined for the oxidation of DTBC to corresponding quinone indicates that they are catalytically quite similar and the kcat of 1 ≈ 2. The crystal structure and the NMR investigations are discussed in detail. 相似文献
926.
Nimmagadda S Geetha Loganathan P Huang R Scaal M Schmidt C Christ B 《Developmental biology》2005,280(1):100-110
Regulation of VEGFR-2 (Quek1) is an important mechanism during blood vessel formation. In the paraxial mesoderm, Quek1 expression is restricted to the lateral portion of the somite and later to sclerotomal cells surrounding the neural tube. By grafting of either intermediate mesoderm or BMP4 beads into the paraxial mesoderm, we show that BMP4 is a positive regulator of VEGFR-2 (Quek1) expression in the quail embryo. Separation of somites from intermediate mesoderm leads to down-regulation of Quek1 expression. The expression of Quek1 in the medial somite half is normally repressed by the notochord and becomes up-regulated and lateromedially expanded after separation of the notochord. Our results show that up-regulation of BMP4 leads to an increase of the number of blood vessels, whereas inhibition of BMP4 by noggin results in a reduction of blood vessels. 相似文献
927.
Ectodermal Wnt-6 promotes Myf5-dependent avian limb myogenesis 总被引:1,自引:0,他引:1
Geetha-Loganathan P Nimmagadda S Pröls F Patel K Scaal M Huang R Christ B 《Developmental biology》2005,288(1):221-233
Limb muscles of vertebrates are derived from precursor cells that migrate from the lateral edge of the dermomyotome into the limb bud. Although several signaling molecules have been reported to be involved in the process of limb myogenesis, none of their activities has led to a consolidate idea about the limb myogenic pathway. Particularly, the role of ectodermal signals in limb myogenesis is still obscure. Here, we investigated the role of the ectoderm and ectodermal Wnt-6 during limb muscle development. We found that ectopic expression of Wnt-6 in the limb bud specifically extends the expression domains of Pax3, Paraxis, Myf5, Myogenin, Desmin and Myosin heavy chain (MyHC) but inhibits MyoD expression. Ectoderm removal results in a loss of expression of all of these myogenic markers. We show that Wnt-6 can compensate the absence of the ectoderm by rescuing the expression of Pax3, Paraxis, Myf5, Myogenin, Desmin and MyHC but not MyoD. These results show that, in chick, at least two signals from the limb ectoderm are necessary for muscle development. One of the signals is Wnt-6, which plays a unique role in promoting limb myogenesis via Pax3/Paraxis-Myf5, whereas the other putative signaling pathway involving MyoD expression is negatively regulated by Wnt-6 signaling. 相似文献
928.
Suramin is a competitive inhibitor of heparin binding to many proteins, including viral envelope proteins, protein tyrosine phosphatases, and fibroblast growth factors (FGFs). It has been clinically evaluated as a potential therapeutic in treatment of cancers caused by unregulated angiogenesis, triggered by FGFs. Although it has shown clinical promise in treatment of several cancers, suramin has many undesirable side effects. There is currently no experimental structure that reveals the molecular interactions responsible for suramin inhibition of heparin binding, which could be of potential use in structure-assisted design of improved analogues of suramin. We report the structure of suramin, in complex with the heparin-binding site of vaccinia virus complement control protein (VCP), which interacts with heparin in a geometrically similar manner to many FGFs. The larger than anticipated flexibility of suramin manifested in this structure, and other details of VCP-suramin interactions, might provide useful structural information for interpreting interactions of suramin with many proteins. 相似文献
929.
Avellar MC Honda L Hamil KG Yenugu S Grossman G Petrusz P French FS Hall SH 《Biology of reproduction》2004,71(5):1453-1460
930.
Vijayvargia R Suresh CG Krishnasastry MV 《Biochemical and biophysical research communications》2004,324(3):1130-1136
The assembly of alpha-HL was shown to rapidly progress upon its interaction with Caveolin-1. Treatment of A431 cells with alpha-HL has resulted in clustering of Caveolin-1 at cell-cell contacts. Consistent with this observation, alpha-HL mutants devoid of assembly property have not induced the clustering of Caveolin-1. While cholesterol depletion of A431 cells completely arrests the assembly of alpha-HL, chelation of membrane cholesterol results in its retarded assembly. Interestingly, HT29 cells, with low Caveolin-1 levels, are resistant to alpha-HL attack. Clustering of Caveolin-1, as seen in case of A431 cells, was readily observed in case of HT29 cells transfected with Caveolin-1 construct, thus overexpressing the full length Caveolin-1, upon alpha-HL treatment. A model was constructed to visualize the interactions between alpha-HL and Caveolin-1 which suggests that facile penetration of alpha-HL's beta-barrel might occur through protein-protein interactions with the surrounding 7 alpha-helices of Caveolin-1. 相似文献