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991.
The dominant cognitive model that accounts for the persistence of delusional beliefs in schizophrenia postulates that patients suffer from a general deficit in belief revision. It is generally assumed that this deficit is a consequence of impaired reasoning skills. However, the possibility that such inflexibility affects the entire system of a patient's beliefs has rarely been empirically tested. Using delusion-neutral material in a well-documented advice-taking task, the present study reports that patients with schizophrenia: 1) revise their beliefs, 2) take into account socially provided information to do so, 3) are not overconfident about their judgments, and 4) show less egocentric advice-discounting than controls. This study thus shows that delusional patients' difficulty in revising beliefs is more selective than had been previously assumed. The specificities of the task and the implications for a theory of delusion formation are discussed. 相似文献
992.
FA Carvalho O Koren JK Goodrich ME Johansson I Nalbantoglu JD Aitken Y Su B Chassaing WA Walters A González JC Clemente TC Cullender N Barnich A Darfeuille-Michaud M Vijay-Kumar R Knight RE Ley AT Gewirtz 《Cell host & microbe》2012,12(2):139-152
Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E.?coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E.?coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis. 相似文献
993.
Hébert L Moumen B Pons N Duquesne F Breuil MF Goux D Batto JM Laugier C Renault P Petry S 《PloS one》2012,7(1):e29953
The Taylorella genus comprises two species: Taylorella equigenitalis, which causes contagious equine metritis, and Taylorella asinigenitalis, a closely-related species mainly found in donkeys. We herein report on the first genome sequence of T. asinigenitalis, analyzing and comparing it with the recently-sequenced T. equigenitalis genome. The T. asinigenitalis genome contains a single circular chromosome of 1,638,559 bp with a 38.3% GC content and 1,534 coding sequences (CDS). While 212 CDSs were T. asinigenitalis-specific, 1,322 had orthologs in T. equigenitalis. Two hundred and thirty-four T. equigenitalis CDSs had no orthologs in T. asinigenitalis. Analysis of the basic nutrition metabolism of both Taylorella species showed that malate, glutamate and alpha-ketoglutarate may be their main carbon and energy sources. For both species, we identified four different secretion systems and several proteins potentially involved in binding and colonization of host cells, suggesting a strong potential for interaction with their host. T. equigenitalis seems better-equipped than T. asinigenitalis in terms of virulence since we identified numerous proteins potentially involved in pathogenicity, including hemagluttinin-related proteins, a type IV secretion system, TonB-dependent lactoferrin and transferrin receptors, and YadA and Hep_Hag domains containing proteins. This is the first molecular characterization of Taylorella genus members, and the first molecular identification of factors potentially involved in T. asinigenitalis and T. equigenitalis pathogenicity and host colonization. This study facilitates a genetic understanding of growth phenotypes, animal host preference and pathogenic capacity, paving the way for future functional investigations into this largely unknown genus. 相似文献
994.
995.
ABSTRACT: BACKGROUND: CADASIL is an autosomal dominant genetic leukoencephalopathy linked to mutations in the Notch3 gene. In rare cases, widespread brain lesions on T2 MRI mimicking multiple sclerosis are observed. From a national registry of 268 patients with adult-onset leukodystrophy, we identified two patients with an atypical presentation of CADASIL without co-occurrence of another systemic disease.Case presentationsPatient 1 experienced progressive gait disability and patient 2 relapsing optic neuritis and sensory-motor deficit in the leg. Both patients responded to corticotherapy and patient 2 was also responsive to glatiramer acetate. No oligoclonal bands were found in the CSF, and MRI showed myelitis and lesions with gadolinium enhancement in brain (patient 1) or incomplete CADASIL phenotype (patient 2). CONCLUSIONS: In rare cases, an inflammatory-like process can occur in CADASIL. In these patients, immunomodulatory treatments, including corticosteroids, could be effective. 相似文献
996.
A Tomaschitz A Fahrleitner-Pammer K Amrein E Ritz BM Pieske K Kienreich JH Horina A Schmidt E Kraigher Krainer A Meinitzer S Pilz C Colantonio N Verheyen 《BMC endocrine disorders》2012,12(1):19
ABSTRACT: BACKGROUND: Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess. Methods/design Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease. The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1--84) as the primary endpoint and (2) 24-hour systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24 hours urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints. DISCUSSION: In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular and bone health in patients with primary hyperparathyroidism. Trial registration ISRCTN33941607. 相似文献
997.
Gautier V Mouton-Barbosa E Bouyssié D Delcourt N Beau M Girard JP Cayrol C Burlet-Schiltz O Monsarrat B Gonzalez de Peredo A 《Molecular & cellular proteomics : MCP》2012,11(8):527-539
To perform differential studies of complex protein mixtures, strategies for reproducible and accurate quantification are needed. Here, we evaluated a quantitative proteomic workflow based on nanoLC-MS/MS analysis on an LTQ-Orbitrap-VELOS mass spectrometer and label-free quantification using the MFPaQ software. In such label-free quantitative studies, a compromise has to be found between two requirements: repeatability of sample processing and MS measurements, allowing an accurate quantification, and high proteomic coverage of the sample, allowing quantification of minor species. The latter is generally achieved through sample fractionation, which may induce experimental bias during the label-free comparison of samples processed, and analyzed independently. In this work, we wanted to evaluate the performances of MS intensity-based label-free quantification when a complex protein sample is fractionated by one-dimensional SDS-PAGE. We first tested the efficiency of the analysis without protein fractionation and could achieve quite good quantitative repeatability in single-run analysis (median coefficient of variation of 5%, 99% proteins with coefficient of variation <48%). We show that sample fractionation by one-dimensional SDS-PAGE is associated with a moderate decrease of quantitative measurement repeatability while largely improving the depth of proteomic coverage. We then applied the method for a large scale proteomic study of the human endothelial cell response to inflammatory cytokines, such as TNFα, interferon γ, and IL1β, which allowed us to finely decipher at the proteomic level the biological pathways involved in endothelial cell response to proinflammatory cytokines. 相似文献
998.
Veyrat-Durebex C Deblon N Caillon A Andrew R Altirriba J Odermatt A Rohner-Jeanrenaud F 《PloS one》2012,7(3):e34002
Glucocorticoids (GCs) are involved in multiple metabolic processes, including the regulation of insulin sensitivity and adipogenesis. Their action partly depends on their intracellular activation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). We previously demonstrated that central GC administration promotes hyperphagia, body weight gain, hyperinsulinemia and marked insulin resistance at the level of skeletal muscles. Similar dysfunctions have been reported to occur upon specific overexpression of 11β-HSD1 in adipose tissue. The aim of the present study was therefore to determine whether the effects of central GC infusion may enhance local GC activation in white adipose tissue. Male Wistar and Sprague Dawley (SD) rats were intracerebroventricularly infused with GCs for 2 to 3 days. Body weight, food intake and metabolic parameters were measured, and expression of enzymes regulating 11β-HSD1, as well as that of genes regulated by GCs, were quantified. Central GC administration induced a significant increase in body weight gain and in 11β-HSD1 and resistin expression in adipose tissue. A decrease 11β-HSD1 expression was noticed in the liver of SD rats, as a partial compensatory mechanism. Such effects of GCs are centrally elicited. This model of icv dexamethasone infusion thus appears to be a valuable acute model, that helps delineating the initial metabolic defects occurring in obesity. An impaired downregulation of intracellular GC activation in adipose tissue may be important for the development of insulin resistance. 相似文献
999.
Vodovar N Bronkhorst AW van Cleef KW Miesen P Blanc H van Rij RP Saleh MC 《PloS one》2012,7(1):e30861
The siRNA pathway is an essential antiviral mechanism in insects. Whether other RNA interference pathways are involved in antiviral defense remains unclear. Here, we report in cells derived from the two main vectors for arboviruses, Aedes albopictus and Aedes aegypti, the production of viral small RNAs that exhibit the hallmarks of ping-pong derived piwi-associated RNAs (piRNAs) after infection with positive or negative sense RNA viruses. Furthermore, these cells produce endogenous piRNAs that mapped to transposable elements. Our results show that these mosquito cells can initiate de novo piRNA production and recapitulate the ping-pong dependent piRNA pathway upon viral infection. The mechanism of viral-piRNA production is discussed. 相似文献
1000.
Schulze-Topphoff U Shetty A Varrin-Doyer M Molnarfi N Sagan SA Sobel RA Nelson PA Zamvil SS 《PloS one》2012,7(3):e33797
Laquinimod is a novel oral drug that is currently being evaluated for the treatment of relapsing-remitting (RR) multiple sclerosis (MS). Using the animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we examined how laquinimod promotes immune modulation. Oral laquinimod treatment reversed established RR-EAE and was associated with reduced central nervous system (CNS) inflammation, decreased Th1 and Th17 responses, and an increase in regulatory T cells (Treg). In vivo laquinimod treatment inhibited donor myelin-specific T cells from transferring EAE to naive recipient mice. In vivo laquinimod treatment altered subpopulations of myeloid antigen presenting cells (APC) that included a decrease in CD11c(+)CD11b(+)CD4(+) dendritic cells (DC) and an elevation of CD11b(hi)Gr1(hi) monocytes. CD11b(+) cells from these mice exhibited an anti-inflammatory type II phenotype characterized by reduced STAT1 phosphorylation, decreased production of IL-6, IL-12/23 and TNF, and increased IL-10. In adoptive transfer, donor type II monocytes from laquinimod-treated mice suppressed clinical and histologic disease in recipients with established EAE. As effects were observed in both APC and T cell compartments, we examined whether T cell immune modulation occurred as a direct effect of laquinimod on T cells, or as a consequence of altered APC function. Inhibition of Th1 and Th17 differentiation was observed only when type II monocytes or DC from laquinimod-treated mice were used as APC, regardless of whether myelin-specific T cells were obtained from laquinimod-treated or untreated mice. Thus, laquinimod modulates adaptive T cell immune responses via its effects on cells of the innate immune system, and may not influence T cells directly. 相似文献