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71.
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73.
ACTH-induced inhibition of endogenous rat brain protein phosphorylation in vitro: Structure activity
Henk Zwiers Victor Marius Wiegant Peter Schotman Willem Hendrik Gispen 《Neurochemical research》1978,3(4):455-463
ACTH1–24 inhibits the endogenous phosphorylation in vitro of distinct SPM protein bands. Using N-terminal fragments of ACTH, the structure-activity requirements for this effect were studied. A rather complex interaction of the ACTH fragments with endogenous SPM phosphorylation was observed. The effects were not only dependent on the primary structure of the peptide used, but also on the protein band studied and the ATP/SPM ratio used in the incubation system. ACTH1–24 did not interfere with the ATP-hydrolyzing activity of the SPM preparation, nor did it influence the endogenous phosphatase activity. Therefore, a direct interaction of ACTH with SPM protein kinase(s) is likely to be responsible for its effect on phosphorylation. 相似文献
74.
Elena Gustchina Mi Li Rodolfo Ghirlando Peter Schuck John M. Louis Jason Pierson Prashant Rao Sriram Subramaniam Alla Gustchina G. Marius Clore Alexander Wlodawer 《PloS one》2013,8(11)
A series of mini-antibodies (monovalent and bivalent Fabs) targeting the conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR) of HIV-1 gp41 has been previously constructed and reported. Crystal structures of two closely related monovalent Fabs, one (Fab 8066) broadly neutralizing across a wide panel of HIV-1 subtype B and C viruses, and the other (Fab 8062) non-neutralizing, representing the extremes of this series, were previously solved as complexes with 5-Helix, a gp41 pre-hairpin intermediate mimetic. Binding of these Fabs to covalently stabilized chimeric trimers of N-peptides of HIV-1 gp41 (named (CCIZN36)3 or 3-H) has now been investigated using X-ray crystallography, cryo-electron microscopy, and a variety of biophysical methods. Crystal structures of the complexes between 3-H and Fab 8066 and Fab 8062 were determined at 2.8 and 3.0 Å resolution, respectively. Although the structures of the complexes with the neutralizing Fab 8066 and its non-neutralizing counterpart Fab 8062 were generally similar, small differences between them could be correlated with the biological properties of these antibodies. The conformations of the corresponding CDRs of each antibody in the complexes with 3-H and 5-Helix are very similar. The adaptation to a different target upon complex formation is predominantly achieved by changes in the structure of the trimer of N-HR helices, as well as by adjustment of the orientation of the Fab molecule relative to the N-HR in the complex, via rigid-body movement. The structural data presented here indicate that binding of three Fabs 8062 with high affinity requires more significant changes in the structure of the N-HR trimer compared to binding of Fab 8066. A comparative analysis of the structures of Fabs complexed to different gp41 intermediate mimetics allows further evaluation of biological relevance for generation of neutralizing antibodies, as well as provides novel structural insights into immunogen design. 相似文献
75.
Caşcaval D Galaction AI Turnea M 《Journal of industrial microbiology & biotechnology》2011,38(9):1449-1466
Study of the distribution of the oxygen mass transfer coefficient, k
l
a, for a stirred bioreactor and simulated (pseudoplastic solutions of carboxymethylcellulose sodium salt) bacterial (P. shermanii), yeast (S. cerevisiae), and fungal (P. chrysogenum free mycelia) broths indicated significant variation of transfer rate with bioreactor height. The magnitude of the influence
of the considered factors differed from one region to another. As a consequence of cell adsorption to bubble surface, the
results indicated the impossibility of achieving a uniform oxygen transfer rate throughout the whole bulk of the microbial
broth, even when respecting the conditions for uniform mixing. Owing to the different affinity of biomass for bubble surface,
the positive influence of power input on k
l
a is more important for fungal broths, while increasing aeration is favorable only for simulated, bacterial and yeast broths.
The influence of the considered factors on k
l
a were included in mathematical correlations established based on experimental data. For all considered positions, the proposed
equations for real broths have the general expression
kl a = aCXb ( \fracPa V )g vSd , k_{\rm l} a = \alpha C_{\rm X}^{\beta } \left( {{\frac{{P_{\rm a} }}{V}}} \right)^{\gamma } v_{\rm S}^{\delta } , exhibiting good agreement with experimental results (with maximum deviations of ±10.7% for simulated broths, ±8.4% for P. shermanii, ±9.3% for S. cerevisiae, and ±6.6% for P. chrysogenum). 相似文献
76.
Van Campenhout CA Eitelhuber A Gloeckner CJ Giallonardo P Gegg M Oller H Grant SG Krappmann D Ueffing M Lickert H 《Developmental cell》2011,21(3):479-491
The Drosophila Discs large (Dlg) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dlg homologs have been identified; however, their functions in cell polarity remain poorly understood. Here, we demonstrate that the X-linked mental retardation gene product Dlg3 contributes to apical-basal polarity and epithelial junction formation in mouse organizer tissues, as well as to planar cell polarity in the inner ear. We purified complexes associated with Dlg3 in polarized epithelial cells, including proteins regulating directed trafficking and tight junction formation. Remarkably, of the four Dlg family members, Dlg3 exerts a distinct function by recruiting the ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs. We found that these interactions are required for Dlg3 monoubiquitination, apical membrane recruitment, and tight junction consolidation. Our findings reveal an unexpected evolutionary diversification of the vertebrate Dlg family in basolateral epithelium formation. 相似文献
77.
Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus 总被引:25,自引:0,他引:25
Stojdl DF Lichty B Knowles S Marius R Atkins H Sonenberg N Bell JC 《Nature medicine》2000,6(7):821-825
Interferons are circulating factors that bind to cell surface receptors, activating a signaling cascade, ultimately leading to both an antiviral response and an induction of growth inhibitory and/or apoptotic signals in normal and tumor cells. Attempts to exploit the ability of interferons to limit the growth of tumors in patients has met with limited results because of cancer-specific mutations of gene products in the interferon pathway. Although interferon-non-responsive cancer cells may have acquired a growth/survival advantage over their normal counterparts, they may have simultaneously compromised their antiviral response. To test this, we used vesicular stomatitis virus (VSV), an enveloped, negative-sense RNA virus exquisitely sensitive to treatment with interferon. VSV rapidly replicated in and selectively killed a variety of human tumor cell lines even in the presence of doses of interferon that completely protected normal human primary cell cultures. A single intratumoral injection of VSV was effective in reducing the tumor burden of nude mice bearing subcutaneous human melanoma xenografts. Our results support the use of VSV as a replication-competent oncolytic virus and demonstrate a new strategy for the treatment of interferon non-responsive tumors. 相似文献
78.
Lötscher M Recher M Lang KS Navarini A Hunziker L Santimaria R Glatzel M Schwarz P Böni J Zinkernagel RM 《PloS one》2007,2(11):e1158
The prion protein (PrP) is crucially involved in transmissible spongiform encephalopathies (TSE), but neither its exact role in disease nor its physiological function are known. Here we show for mice, using histological, immunochemical and PCR-based methods, that stimulation of innate resistance was followed by appearance of numerous endogenous retroviruses and ensuing PrP up-regulation in germinal centers of the spleen. Subsequently, the activated retroviruses disappeared in a PrP-dependent manner. Our results reveal the regular involvement of endogenous retroviruses in murine immune responses and provide evidence for an essential function of PrP in the control of the retroviral activity. The interaction between PrP and ubiquitous endogenous retroviruses may allow new interpretations of TSE pathophysiology and explain the evolutionary conservation of PrP. 相似文献
79.
M. Christiane Brahimi-Horn Sandra Lacas-Gervais Ricardo Adaixo Karine Ilc Matthieu Rouleau Annick Notte Marc Dieu Carine Michiels Thibault Voeltzel Vronique Maguer-Satta Joffrey Pelletier Marius Ilie Paul Hofman Bndicte Manoury Alexander Schmidt Sebastian Hiller Jacques Pouyssgur Nathalie M. Mazure 《Molecular and cellular biology》2022,42(1)
80.
Rogerio Pessoto Hirata Tanja Schj?dt J?rgensen Sara Rosager Lars Arendt-Nielsen Henning Bliddal Marius Henriksen Thomas Graven-Nielsen 《PloS one》2013,8(8)