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991.
Kunnambath Ramadas Catherine Sauvaget Gigi Thomas Jean-Marie Fayette Somanathan Thara Rengaswamy Sankaranarayanan 《Cancer epidemiology》2010,34(4):405-412
Objective: To study the risk of all-cause, cancer and tobacco-related cancer mortality associated with tobacco chewing, tobacco smoking and alcohol use. Design: Prospective community-based cohort study initiated in 1996. Participants: 167 343 adult subjects, aged 34 and older, living in 13 panchayaths (rural municipal administrative units) in South India, were regularly followed-up for a mean duration of 6.5 years. Main outcome measures: Mortality from all-causes, all cancer and tobacco-related cancer. Results: The mortality risks associated with chewing (and 95% confidence intervals), after adjusting for age, sex, socio-economic and dietary variables, and for other habits, were 0.90 (0.86–0.94) for all-cause, 1.07 (0.94–1.22) for cancer and 1.22 (1.04–1.44) for tobacco-related cancer; with smoking the respective mortality risks were 1.31 (1.24–1.39), 1.63 (1.37–1.94) and 1.68 (1.36–2.08); and with alcohol use the risks were 1.13 (1.06–1.20), 1.32 (1.11–1.57) and 1.47 (1.19–1.80), respectively. Reduced risk of all-cause mortality by chewing was observed only in the 60–84 years old group (0.90 (0.85–0.94)), and detrimental effects of chewing on cancer mortality were shown in the young and middle-age groups: 34–39 years old (1.33 (0.67–2.65)), and 40–59 years old (1.26 (1.03–1.55)). Conclusion: Tobacco in any form and alcohol uses were harmful and a higher quality of life could be achieved by avoiding these habits. Given the demographic, epidemiological and economic transitions and changes in pattern of tobacco and alcohol use in India, the health loss from the tobacco and alcohol will grow even larger, unless effective interventions and policies to reduce these habits are implemented. 相似文献
992.
Fatma Daoud Aurora Candelario-Martínez Jean-Marie Billard Avi Avital Malik Khelfaoui Yael Rozenvald Maryvonne Guegan Dominique Mornet Danielle Jaillard Uri Nudel Jamel Chelly Dalila Martínez-Rojas Serge Laroche David Yaffe Cyrille Vaillend 《PloS one》2009,4(8)
Background
Duchenne muscular dystrophy (DMD) is caused by deficient expression of the cytoskeletal protein, dystrophin. One third of DMD patients also have mental retardation (MR), likely due to mutations preventing expression of dystrophin and other brain products of the DMD gene expressed from distinct internal promoters. Loss of Dp71, the major DMD-gene product in brain, is thought to contribute to the severity of MR; however, the specific function of Dp71 is poorly understood.Methodology/Principal Findings
Complementary approaches were used to explore the role of Dp71 in neuronal function and identify mechanisms by which Dp71 loss may impair neuronal and cognitive functions. Besides the normal expression of Dp71 in a subpopulation of astrocytes, we found that a pool of Dp71 colocalizes with synaptic proteins in cultured neurons and is expressed in synaptic subcellular fractions in adult brains. We report that Dp71-associated protein complexes interact with specialized modular scaffolds of proteins that cluster glutamate receptors and organize signaling in postsynaptic densities. We then undertook the first functional examination of the brain and cognitive alterations in the Dp71-null mice. We found that these mice display abnormal synapse organization and maturation in vitro, altered synapse density in the adult brain, enhanced glutamatergic transmission and reduced synaptic plasticity in CA1 hippocampus. Dp71-null mice show selective behavioral disturbances characterized by reduced exploratory and novelty-seeking behavior, mild retention deficits in inhibitory avoidance, and impairments in spatial learning and memory.Conclusions/Significance
Results suggest that Dp71 expression in neurons play a regulatory role in glutamatergic synapse organization and function, which provides a new mechanism by which inactivation of Dp71 in association with that of other DMD-gene products may lead to increased severity of MR. 相似文献993.
Stéphane Doly Jesus Bertran-Gonzalez Jacques Callebert Alexandra Bruneau Sophie Marie Banas Arnauld Belmer Katia Boutourlinsky Denis Hervé Jean-Marie Launay Luc Maroteaux 《PloS one》2009,4(11)
The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) reverses dopamine and serotonin transporters to produce efflux of dopamine and serotonin, respectively, in regions of the brain that have been implicated in reward. However, the role of serotonin/dopamine interactions in the behavioral effects of MDMA remains unclear. We previously showed that MDMA-induced locomotion, serotonin and dopamine release are 5-HT2B receptor-dependent. The aim of the present study was to determine the contribution of serotonin and 5-HT2B receptors to the reinforcing properties of MDMA.We show here that 5-HT2B
−/− mice do not exhibit behavioral sensitization or conditioned place preference following MDMA (10 mg/kg) injections. In addition, MDMA-induced reinstatement of conditioned place preference after extinction and locomotor sensitization development are each abolished by a 5-HT2B receptor antagonist (RS127445) in wild type mice. Accordingly, MDMA-induced dopamine D1 receptor-dependent phosphorylation of extracellular regulated kinase in nucleus accumbens is abolished in mice lacking functional 5-HT2B receptors. Nevertheless, high doses (30 mg/kg) of MDMA induce dopamine-dependent but serotonin and 5-HT2B receptor-independent behavioral effects.These results underpin the importance of 5-HT2B receptors in the reinforcing properties of MDMA and illustrate the importance of dose-dependent effects of MDMA on serotonin/dopamine interactions. 相似文献
994.
Petra Gromova Sebastian Ralea Anne Lefort Frédérick Libert Brian P Rubin Christophe Erneux Jean-Marie Vanderwinden 《Journal of cellular and molecular medicine》2009,13(8A):1536-1548
Gastrointestinal stromal tumours (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the receptor tyrosine kinase KIT are present in most GIST. KIT K642E was originally identified in sporadic GIST and later found in the germ line of a familial GIST cohort. A mouse model harbouring a germline Kit K641E mutant was created to model familial GIST. The expression profile was investigated in the gastric antrum of the Kit K641E murine GIST model by microarray, quantitative PCR and immunofluorescence. Gja1/Cx43 , Gpc6 , Gpr133 , Pacrg , Pde3a , Prkar2b , Prkcq/Pkce , Rasd2 , Spry4 and Tpbg/5T4 were found to be up-regulated. The proteins encoded by Gja1/Cx43 , Pde3a , Prkcq/Pkce were localized in Kit-ir ICC in wild-type and Kit K641E animals while Spry4 and Tpbg/5T4 were detected in Kit-ir cells only in Kit K641E , but not in Kit WT/WT animals. Most up-regulated genes in this mouse model belong to the gene expression profile of human GIST but also to the profile of normal Kit+ ICC in the mouse small intestine. Spry4 and Tpbg/5T4 may represent candidates for targeted therapeutic approaches in GIST with oncogenic KIT mutations. 相似文献
995.
Genetic Diversity and Quinolone Resistance in Campylobacter jejuni Isolates from Poultry in Senegal 总被引:2,自引:0,他引:2 下载免费PDF全文
Alfred Dieudonn Kinana Eric Cardinale Fatou Tall Ibrahim Bahsoun Jean-Marie Sire Benoit Garin Sebastien Breurec Cheikh Saad-Bouh Boye Jean-David Perrier-Gros-Claude 《Applied microbiology》2006,72(5):3309-3313
We used the multilocus sequence typing (MLST) method to evaluate the genetic diversity of 46 Campylobacter jejuni isolates from chickens and to determine the link between quinolone resistance and sequence type (ST). There were a total of 16 ST genotypes, and the majority of them belonged to seven clonal complexes previously identified by using isolates from human disease. The ST-353 complex was the most common complex, whereas the ST-21, ST-42, ST-52, and ST-257 complexes were less well represented. The resistance phenotype varied for each ST, and the Thr-86-Ile substitution in the GyrA protein was the predominant mechanism of resistance to quinolone. Nine of the 14 isolates having the Thr-86-Ile substitution belonged to the ST-353 complex. MLST showed that the emergence of quinolone resistance is not related to the diffusion of a unique clone and that there is no link between ST genotype and quinolone resistance. Based on silent mutations, different variants of the gyrA gene were shown to exist for the same ST. These data provide useful information for understanding the epidemiology of C. jejuni in Senegal. 相似文献
996.
997.
Rejraji H Sion B Prensier G Carreras M Motta C Frenoux JM Vericel E Grizard G Vernet P Drevet JR 《Biology of reproduction》2006,74(6):1104-1113
We have isolated vesicular structures from mouse epididymal fluid, referred to as epididymosomes. Epididymosomes have a roughly spherical aspect and a bilayer membrane, and they are heterogeneous in size and content. They originate from the epididymal epithelium, notably from the caput region, and are emitted in the epididymal lumen by way of apocrine secretion. We characterized their membranous lipid profiles in caput and cauda epididymidal fluid samples and found that epididymosomes were particularly rich in sphingomyelin (SM) and arachidonic acid. The proportion of SM increased markedly during epididymal transit and represented half the total phospholipids in cauda epididymidal epididymosomes. The cholesterol:phospholipid ratio increased from 0.26 in the caput to 0.48 in the cauda epididymidis. Measures of epididymosomal membrane anisotropy revealed that epididymosomes became more rigid during epididymal transit, in agreement with their lipid composition. In addition, we have characterized the membrane lipid pattern of murine epididymal spermatozoa during their maturation. Here, we have shown that mouse epididymal spermatozoa were distinguished by high percentages of SM and polyunsaturated membranous fatty acids (PUFAs), principally represented by arachidonic, docosapentanoic, and docosahexanoic acids. Both SM and PUFA increased throughout the epididymal tract. In particular, we observed a threefold rise in the ratio of docosapentanoic acid. Epididymal spermatozoa had a constant cholesterol:phospholipid ratio (average, 0.30) during epididymal transit. These data suggest that in contrast with epididymosomes, spermatozoal membranes seem to become more fluid during epididymal maturation. 相似文献
998.
Anne Baudry Juliette Bitard Sophie Mouillet-Richard Morgane Locker Anne Poliard Jean-Marie Launay Odile Kellermann 《The Journal of biological chemistry》2010,285(34):26066-26073
In previous studies, we observed that mice knocked out for the serotonin-2B receptor (5-HT2BR) show defects in bone homeostasis. The present work focuses on the downstream targets relaying the anabolic function of this receptor in osteoblasts. A functional link between the 5-HT2BR and the activity of the tissue-nonspecific alkaline phosphatase (TNAP) is established using the C1 osteoprogenitor cell line. During C1 osteogenic differentiation, both 5-HT2BR and TNAP mRNA translations are delayed with respect to extracellular matrix deposition. Once the receptor is expressed, it constitutively controls TNAP activity at a post-translational level along the overall period of mineral deposition. Indeed, pharmacological inhibition of the 5-HT2BR intrinsic activity or shRNA-mediated 5-HT2BR knockdown prevents TNAP activation, but not its mRNA translation. In contrast, agonist stimulation of the receptor further increases TNAP activity during the initial mineralization phase. Building upon our previous observations that the 5-HT2BR couples with the phospholipase A2 pathway and prostaglandin production at the beginning of mineral deposition, we show that the 5-HT2BR controls leukotriene synthesis via phospholipase A2 at the terminal stages of C1 differentiation. These two 5-HT2BR-dependent eicosanoid productions delineate distinct time windows of TNAP regulation during the osteogenic program. Finally, prostaglandins or leukotrienes are shown to relay the post-translational activation of TNAP via stimulation of the phosphatidylinositol-specific phospholipase C. In agreement with the above findings, primary calvarial osteoblasts from 5-HT2BR-null mice exhibit defects in TNAP activity. 相似文献
999.
Frédéric Kerff Frédéric Mercier Raphaël Herman Astrid Zervosen Jean-Marie Frère Paulette Charlier 《Journal of molecular biology》2010,397(1):249-34403
AmiD is the fifth identified N-acetylmuramoyl-l-alanine zinc amidase of Escherichia coli. This periplasmic lipoprotein is anchored in the outer membrane and has a broad specificity. AmiD is capable of cleaving the intact peptidoglycan (PG) as well as soluble fragments containing N-acetylmuramic acid regardless of the presence of an anhydro form or not, unlike the four other amidases, AmiA, AmiB, AmiC, and AmpD, which have some specificity. AmiD function is, however, not clearly established but it could be part of the enzymatic machinery involved in the PG turnover in E. coli. We solved three structures of the E. coli zinc amidase AmiD devoid of its lipidic anchorage: the holoenzyme, the apoenzyme in complex with the substrate anhydro-N-acetylmuramic-acid-l-Ala-γ-d-Glu-l-Lys, and the holoenzyme in complex with the l-Ala-γ-d-Glu-l-Lys peptide, the product of the hydrolysis of this substrate by AmiD. The AmiD structure shows a relatively flexible N-terminal extension that allows an easy reach of the PG by the enzyme inserted into the outer membrane. The C-terminal domain provides a potential extended geometrical complementarity to the substrate. AmiD shares a common fold with AmpD, the bacteriophage T7 lysozyme, and the PG recognition proteins, which are receptor proteins involved in the innate immune responses of a wide range of organisms. Analysis of the different structures reveals the similarity between the catalytic mechanism of zinc amidases of the AmiD family and the thermolysin-related zinc peptidases. 相似文献
1000.
Schatz B Geoffroy A Dainat B Bessière JM Buatois B Hossaert-McKey M Selosse MA 《American journal of botany》2010,97(8):1278-1288
? Premise of the study: Most studies on orchid hybrids examine separately the effects of hybridization on interactions with pollinators or with mycorrhizal fungi. Here, we simultaneously investigated both interactions in the mediterranean food-deceptive Orchis simia, O. anthropophora, and their hybrid (O. ×bergonii) and tested a possible breakdown of coevolution using a multidisciplinary approach. ? Methods: We compared leaf growth, seed viability, emitted scent, and mycorrhizal fungi (species and rate of infection) among these three taxa. ? Key results: We show that leaf surface is greater in adult hybrids than in the parental species, suggesting a heterosis effect for vegetative growth. We demonstrate that flowers of the two parental species emit well-differentiated bouquets of volatile organic compounds, while hybrids emit larger quantities, accumulating most compounds of the two parental species. However, hybrids fail to attract pollinators and have a 10 times lower fruit set. We determined that closely related Tulasnellales are mycorrhizal in the three taxa, suggesting that the mycorrhizal partner does not impair hybrid survival. We propose an interpretative model for O. ×bergonii compared with its parents. ? Conclusions: In hybrids, carbon resources normally devoted to reproduction may be reallocated to the mycorrhizal symbiosis as a result of the disruption of the pollination interaction in hybrids. Higher mycorrhizal infection may in turn enhance vegetative growth and scent emission. Such interplay between the two obligate biotic interactions yields new insights into hybridization among orchids. 相似文献