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91.
All identified membrane fusion proteins are transmembrane proteins. In the present study, we explored the post-mitotic reassembly of the NE (nuclear envelope). The proteins that drive membrane rearrangements in NE assembly remain unknown. To determine whether transmembrane proteins are prerequisite components of this fusion machinery, we have focused on nuclear reconstitution in a cell-free system. Mixing of soluble interphase cytosolic extract and MV (membrane vesicles) from amphibian eggs with chromatin results in the formation of functional nuclei. We replaced MV and cytosol with protein-free phosphatidylcholine LS (liposomes) that were pre-incubated with interphase cytosol. While later stages of NE assembly yielding functional nucleus did not proceed without integral proteins of MV, LS-associated cytosolic proteins were sufficient to reconstitute membrane targeting to the chromatin and GTP-dependent lipid mixing. Binding involved LS-associated A-type lamin, and fusion involved Ran GTPase. Thus in contrast with post-fusion stages, fusion initiation in NE assembly, like membrane remodelling in budding and fission, does not require transmembrane proteins. 相似文献
92.
Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome
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Huebner A Mann P Rohde E Kaindl AM Witt M Verkade P Jakubiczka S Menschikowski M Stoltenburg-Didinger G Koehler K 《Molecular and cellular biology》2006,26(5):1879-1887
Triple A syndrome is a human autosomal recessive disorder characterized by adrenal insufficiency, achalasia, alacrima, and neurological abnormalities affecting the central, peripheral, and autonomic nervous systems. In humans, this disease is caused by mutations in the AAAS gene, which encodes ALADIN, a protein that belongs to the family of WD-repeat proteins and localizes to nuclear pore complexes. To analyze the function of the gene in the context of the whole organism and in an attempt to obtain an animal model for human triple A syndrome, we generated mice lacking a functional Aaas gene. The Aaas-/- animals were found to be externally indistinguishable from their wild-type littermates, although their body weight was on the average lower than that of wild-type mice. Histological analysis of various tissues failed to reveal any differences between Aaas-/- and wild-type mice. Aaas-/- mice exhibit unexpectedly mild abnormal behavior and only minor neurological deficits. Our data show that the lack of ALADIN in mice does not lead to a triple A syndrome-like disease. Thus, in mice either the function of ALADIN differs from that in humans, its loss can be readily compensated for, or additional factors, such as environmental conditions or genetic modifiers, contribute to the disease. 相似文献
93.
Veshkurova O Golubenko Z Pshenichnov E Arzanova I Uzbekov V Sultanova E Salikhov S Williams HJ Reibenspies JH Puckhaber LS Stipanovic RD 《Phytochemistry》2006,67(21):2376-2379
The isolation and structure of a phytoalexin, malvone A (2-methyl-3-methoxy-5,6-dihydroxy-1,4-naphthoquinone) is reported. Malvone A formation is induced in Malva sylvestris L. by the plant pathogen Verticillium dahliae. In a turbimetric assay for toxicity to V. dahliae, it had an ED50 value of 24 microg/ml. The structure of malvone A was determined by MS and NMR spectroscopy, and by X-ray crystallographic analysis. The X-ray analysis showed water molecules were located in channels that run along the a-axis. 相似文献
94.
Evidence that low doses of Taxol enhance the functional transactivatory properties of p53 on p21 waf promoter in MCF-7 breast cancer cells 总被引:2,自引:0,他引:2
Panno ML Giordano F Mastroianni F Morelli C Brunelli E Palma MG Pellegrino M Aquila S Miglietta A Mauro L Bonofiglio D Andò S 《FEBS letters》2006,580(9):2371-2380
In the present study, we evidence how in breast cancer cells low doses of Taxol for 18 h determined the upregulation of p53 and p21 waf expression concomitantly with a decrease of the anti-apoptotic Bcl-2. P53 and its gene product, the mdm2 protein, in treated cells exhibits a prevalent nuclear compartmentalization, thus potentiating p53 transactivatory properties. Indeed, the most important finding of this study consists with the evidence that Taxol at lower concentrations is able to produce the activation of p21 promoter via p53. Prolonged exposure of MCF-7 cells to Taxol (48 h) resulted in an increased co-association between p21 and PCNA compared to control and this well fits with the simultaneous block of cell cycle into the G2/M phase. 相似文献
95.
Rossi AG Sawatzky DA Walker A Ward C Sheldrake TA Riley NA Caldicott A Martinez-Losa M Walker TR Duffin R Gray M Crescenzi E Martin MC Brady HJ Savill JS Dransfield I Haslett C 《Nature medicine》2006,12(9):1056-1064
Apoptosis is essential for clearance of potentially injurious inflammatory cells and subsequent efficient resolution of inflammation. Here we report that human neutrophils contain functionally active cyclin-dependent kinases (CDKs), and that structurally diverse CDK inhibitors induce caspase-dependent apoptosis and override powerful anti-apoptosis signals from survival factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF). We show that the CDK inhibitor R-roscovitine (Seliciclib or CYC202) markedly enhances resolution of established neutrophil-dependent inflammation in carrageenan-elicited acute pleurisy, bleomycin-induced lung injury, and passively induced arthritis in mice. In the pleurisy model, the caspase inhibitor zVAD-fmk prevents R-roscovitine-enhanced resolution of inflammation, indicating that this CDK inhibitor augments inflammatory cell apoptosis. We also provide evidence that R-roscovitine promotes apoptosis by reducing concentrations of the anti-apoptotic protein Mcl-1. Thus, CDK inhibitors enhance the resolution of established inflammation by promoting apoptosis of inflammatory cells, thereby demonstrating a hitherto unrecognized potential for the treatment of inflammatory disorders. 相似文献
96.
97.
Hurtado-Carneiro V Sanz C Roncero I Vazquez P Blazquez E Alvarez E 《Molecular neurobiology》2012,45(2):348-361
The anorexigenic peptide, glucagon-like peptide-1 (GLP-1), reduces glucose metabolism in the human hypothalamus and brain
stem. The brain activity of metabolic sensors such as AMP-activated protein kinase (AMPK) responds to changes in glucose levels.
The mammalian target of rapamycin (mTOR) and its downstream target, p70S6 kinase (p70S6K), integrate nutrient and hormonal
signals. The hypothalamic mTOR/p70S6K pathway has been implicated in the control of feeding and the regulation of energy balances.
Therefore, we investigated the coordinated effects of glucose and GLP-1 on the expression and activity of AMPK and p70S6K
in the areas involved in the control of feeding. The effect of GLP-1 on the expression and activities of AMPK and p70S6K was
studied in hypothalamic slice explants exposed to low- and high-glucose concentrations by quantitative real-time RT-PCR and
by the quantification of active-phosphorylated protein levels by immunoblot. In vivo, the effects of exendin-4 on hypothalamic
AMPK and p70S6K activation were analysed in male obese Zucker and lean controls 1 h after exendin-4 injection to rats fasted
for 48 h or after re-feeding for 2–4 h. High-glucose levels decreased the expression of Ampk in the lateral hypothalamus and treatment with GLP-1 reversed this effect. GLP-1 treatment inhibited the activities of AMPK
and p70S6K when the activation of these protein kinases was maximum in both the ventromedial and lateral hypothalamic areas.
Furthermore, in vivo s.c. administration of exendin-4 modulated AMPK and p70S6K activities in those areas, in both fasted
and re-fed obese Zucker and lean control rats. 相似文献
98.
99.
Danubio ME Sanna E Rufo F Martorella D Vecchi E Coppa A 《Human biology; an international record of research》2012,84(2):153-167
This study analyzed the variations in space of 8 body dimensions and 11 measures of the head of 1,244 adult Yemenite males, collected in 1933/34 by Coon in Yemen and in Hadhramawt. The aim was to evaluate the presence of geographic microdifferentiation of the populations settled in the different regions of Yemen at the time. Coon sub-divided the sample into six geographical areas according to birthplace and ethnicity of the individuals: Tihamah, the Western Mountains, the Central Plateau, the South Coast, the Eastern Mountains, and Hadhramawt. The results of ANCOVA (age as covariate) show that the observed differences of all variables among the six groups were highly statistically significant. Tukey's post-hoc test reveals higher statistically significant differences among four main groups: (1) Tihamah; (2) the Western Mountains and Central Plateau; (3) the Eastern Mountains; and (4) the Southern Coast and Hadhramawt. Multiple discriminant analysis carried out using only the data of the 11 measures of the head, the more "genetically" determined variables, confirmed these differences. Indeed, the first canonical variate well separates the groups with the Tihamah, Southern Coast and Hadhramawt on the one side and the Eastern Mountains, Western Mountains and Central Plateau on the other. The second canonical variate separates the Tihamah, Western Mountains and Central Plateau from the Eastern Mountains, Southern Coast and Hadhramawt. In conclusion, the Yemenite population seems to be composed of three morphologically distinct groups and an Eastern Mountains group which is positioned between the group formed by the Southern Coast and Hadhramawt and the Western Mountains and Central Plateau group. The Tihamah is the most distant from all the other groups. These differences are probably due to the presence/absence of geographical and cultural barriers that have favored/blocked the gene flow over the years. Indeed, the entire coastal bell, through the centuries, has constituted one of the principal commercial routes between the East, Africa, and the eastern Mediterranean, while the high inland mountains have isolated the remaining communities. This data is also confirmed by genetic studies. Finally, the average height (162.6 cm) of the global Yemenite population, compared to data from the other six middle-eastern Arab countries and Egypt, was found to be 3-6 cm less. This characteristic will be further studied, analyzing variations in average height according to the different age classes in order to evaluate any possible secular changes. 相似文献
100.
Hebert EM Saavedra L Taranto MP Mozzi F Magni C Nader ME Font de Valdez G Sesma F Vignolo G Raya RR 《Journal of bacteriology》2012,194(2):538-539
Lactobacillus curvatus is one of the most prevalent lactic acid bacteria found in fermented meat products. Here, we present the draft genome sequence of Lactobacillus curvatus CRL705, a bacteriocin producer strain isolated from an Argentinean artisanal fermented sausage, which consists of 1,833,251 bp (GC content, 41.9%) and two circular plasmids of 12,342 bp (pRC12; GC, 43.9%) and 18,664 bp (pRC18; GC, 34.4%). 相似文献