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991.
K Chemin A Bohineust S Dogniaux M Tourret S Guégan F Miro C Hivroz 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(5):2159-2168
Cytokine secretion by T lymphocytes plays a central role in mounting adaptive immune responses. However, little is known about how newly synthesized cytokines, once produced, are routed within T cells and about the mechanisms involved in regulating their secretions. In this study, we investigated the role of cytoskeleton remodeling at the immunological synapse (IS) in cytokine secretion. We show that a key regulator of cytoskeleton remodeling, the Rho GTPase Cdc42, controls IFN-γ secretion by primary human CD4(+) T lymphocytes. Surprisingly, microtubule organizing center polarity at the IS, which does not depend on Cdc42, is not required for cytokine secretion by T lymphocytes, whereas microtubule polymerization is required. In contrast, actin remodeling at the IS, which depends on Cdc42, controls the formation of the polymerized actin ring at the IS, the dynamic concentration of IFN-γ-containing vesicles inside this ring, and the secretion of these vesicles. These results reveal a previously unidentified role of Cdc42-dependent actin remodeling in cytokine exocytosis at the IS. 相似文献
992.
Arsac LM Nouette-Gaulain K Miraux S Deschodt-Arsac V Rossignol R Thiaudiere E Diolez P 《The Biochemical journal》2012,444(2):315-321
Bupivacaine is a widely used anaesthetic injected locally in clinical practice for short-term neurotransmission blockade. However, persistent side effects on mitochondrial integrity have been demonstrated in muscle parts surrounding the injection site. We use the precise language of metabolic control analysis in the present study to describe in vivo consequences of bupivacaine injection on muscle energetics during contraction. We define a model system of muscle energy metabolism in rats with a sciatic nerve catheter that consists of two modules of reactions, ATP/PCr (phosphocreatine) supply and ATP/PCr demand, linked by the common intermediate PCr detected in vivo by (31)P-MRS (magnetic resonance spectroscopy). Measured system variables were [PCr] (intermediate) and contraction (flux). We first applied regulation analysis to quantify acute effects of bupivacaine. After bupivacaine injection, contraction decreased by 15.7% and, concomitantly, [PCr] increased by 11.2%. The regulation analysis quantified that demand was in fact directly inhibited by bupivacaine (-21.3%), causing an increase in PCr. This increase in PCr indirectly reduced mitochondrial activity (-22.4%). Globally, the decrease in contractions was almost fully explained by inhibition of demand (-17.0%) without significant effect through energy supply. Finally we applied elasticity analysis to quantify chronic effects of bupivacaine iterative injections. The absence of a difference in elasticities obtained in treated rats when compared with healthy control rats clearly shows the absence of dysfunction in energetic control of muscle contraction energetics. The present study constitutes the first and direct evidence that bupivacaine myotoxicity is compromised by other factors during contraction in vivo, and illustrates the interest of modular approaches to appreciate simple rules governing bioenergetic systems when affected by drugs. 相似文献
993.
994.
995.
El Bouzidi L Abbad A Hassani L Fattarsi K Leach D Markouk M Legendre L Bekkouche K 《Chemistry & biodiversity》2012,9(3):598-605
The essential oils of leaves and flowers of the wild and cultivated Moroccan Achillea ageratum L., a rare and threatened medicinal species, were examined by GC/MS, and their chemical compositions were compared. At least nine components were identified in both wild and cultivated A. ageratum oils, representing more than 95% of the oils. Artemisyl acetate (62.34-78.79%), yomogi alcohol (4.89-12.40%), santolina alcohol (4.86-11.77%), and artemisia alcohol (3.36-7.04%) were the major compounds. Terpene-alcohol proportion was higher in wild A. ageratum than in cultivated A. ageratum. The antibacterial analysis showed that both oils presented high activity against all the studied Gram-positive strains in a range of MIC values from 2.55 to 7.02?mg/ml, but they appeared not effective against the tested Gram-negative ones (MIC values 20.40-41.10?mg/ml). They also exhibited remarkable antifungal activities against Candida species with MIC values ranging from 5.83 to 8.42?mg/ml. From these results, it was concluded that domestication of this threatened medicinal species using clonal propagation did not significantly affect its chemical composition and consequently its antimicrobial properties. 相似文献
996.
Marie Chabault Elisabeth Baéza Vérane Gigaud Pascal Chartrin Hervé Chapuis Maryse Boulay Cécile Arnould Fran?ois D’Abbadie Cécile Berri Elisabeth Le Bihan-Duval 《BMC genetics》2012,13(1):1-8
Background
Extensive genome-wide analyses of many human populations, using microarrays containing hundreds of thousands of single-nucleotide polymorphisms, have provided us with abundant information about global genomic diversity. However, these data can also be used to analyze local variability in individual genomic regions. In this study, we analyzed the variability in two genomic regions carrying the genes of the GSTA and GSTM subfamilies, located on different chromosomes.Results
Analysis of the polymorphisms in GSTA and GSTM gene clusters showed similarities in their allelic and haplotype diversities. These patterns were similar in three Russian populations and the CEU population of European origin. There were statistically significant differences in all the haploblocks of both the GSTM and GSTA regions when the Russian populations were compared with populations from China and Japan. Most haploblocks also differed between the Russians and Nigerians from Yoruba, but, some of them had similar allelic frequencies. Special attention was paid to SNP rs4986947 from the intron of the GSTA4 gene, which is represented in apes by an A nucleotide. In the Asian and African samples, it was represented only by a G allele, and both allelic variants (G/A) occurred in the Russian and European populations.Conclusions
The results obtained suggest the presence of common features in the evolutionary histories of the GSTA and GSTM gene regions, and that African subpopulations were involved differently in the formation of the European and Asian human lineages. 相似文献997.
Kratz JM Teixeira MR Ferronato K Teixeira HF Koester LS Simões CM 《AAPS PharmSciTech》2012,13(1):118-124
Thalidomide is emerging as a therapeutic agent with renewed clinical importance, presenting anti-inflammatory, immunomodulatory,
and antineoplasic properties. In this work, we studied the complexation of thalidomide with cyclodextrins as a strategy to
circumvent the poor aqueous solubility of the drug. Thalidomide–hydroxypropyl-β-cyclodextrin complexes were obtained by kneading
method and were characterized by differential scanning calorimetry, powder X-ray diffractometry, and scanning electronic microscopy.
The aqueous solubility and in vitro dissolution of thalidomide were significantly improved through the complexation. Physicochemical analysis of the complexes
in solid state revealed a decreased crystallinity of the complexed drug in comparison with free thalidomide. Thalidomide was
able to dissociate from the complexes and permeates across intestinal epithelial Caco-2 cells with a favorable high permeability
profile equivalent to that of the free drug. In summary, the present results suggest that thalidomide–hydroxypropyl-β-cyclodextrin
complexes could be regarded as a promising strategy for improving the gastrointestinal absorption of thalidomide. 相似文献
998.
Uchime O Herrera R Reiter K Kotova S Shimp RL Miura K Jones D Lebowitz J Ambroggio X Hurt DE Jin AJ Long C Miller LH Narum DL 《Eukaryotic cell》2012,11(5):615-625
Thrombospondin repeat (TSR)-like domains are structures involved with cell adhesion. Plasmodium falciparum proteins containing TSR domains play crucial roles in parasite development. In particular, the preerythrocytic P. falciparum circumsporozoite protein is involved in hepatocyte invasion. The importance of these domains in two other malaria proteins, the merozoite-specific thrombospondin-related anonymous protein (MTRAP) and the thrombospondin-related apical membrane protein (PTRAMP), were assessed using near-full-length recombinant proteins composed of the extracellular domains produced in Escherichia coli. MTRAP is thought to be released from invasive organelles identified as micronemes during merozoite invasion to mediate motility and host cell invasion through an interaction with aldolase, an actin binding protein involved in the moving junction. PTRAMP function remains unknown. In this study, the conformation of recombinant MTRAP (rMTRAP) appeared to be a highly extended protein (2 nm by 33 nm, width by length, respectively), whereas rPTRAMP had a less extended structure. Using an erythrocyte binding assay, rMTRAP but not rPTRAMP bound human erythrocytes; rMTRAP binding was mediated through the TSR domain. MTRAP- and in general PTRAMP-specific antibodies failed to inhibit P. falciparum development in vitro. Altogether, MTRAP is a highly extended bifunctional protein that binds to an erythrocyte receptor and the merozoite motor. 相似文献
999.
Ismail Iraqui Yasmina Chekkal Nada Jmari Violena Pietrobon Karine Fréon Audrey Costes Sarah A. E. Lambert 《PLoS genetics》2012,8(10)
Homologous recombination is a universal mechanism that allows repair of DNA and provides support for DNA replication. Homologous recombination is therefore a major pathway that suppresses non-homology-mediated genome instability. Here, we report that recovery of impeded replication forks by homologous recombination is error-prone. Using a fork-arrest-based assay in fission yeast, we demonstrate that a single collapsed fork can cause mutations and large-scale genomic changes, including deletions and translocations. Fork-arrest-induced gross chromosomal rearrangements are mediated by inappropriate ectopic recombination events at the site of collapsed forks. Inverted repeats near the site of fork collapse stimulate large-scale genomic changes up to 1,500 times over spontaneous events. We also show that the high accuracy of DNA replication during S-phase is impaired by impediments to fork progression, since fork-arrest-induced mutation is due to erroneous DNA synthesis during recovery of replication forks. The mutations caused are small insertions/duplications between short tandem repeats (micro-homology) indicative of replication slippage. Our data establish that collapsed forks, but not stalled forks, recovered by homologous recombination are prone to replication slippage. The inaccuracy of DNA synthesis does not rely on PCNA ubiquitination or trans-lesion-synthesis DNA polymerases, and it is not counteracted by mismatch repair. We propose that deletions/insertions, mediated by micro-homology, leading to copy number variations during replication stress may arise by progression of error-prone replication forks restarted by homologous recombination. 相似文献
1000.
Karine Baumstarck Fran?oise Reuter Mohamed Boucekine Valérie Aghababian Irina Klemina Anderson Loundou Jean Pelletier Pascal Auquier 《PloS one》2012,7(12)