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991.
Fehér Á Juhász A László A Kálmán J Pákáski M Kálmán J Janka Z 《Neuroscience letters》2012,517(2):136-139
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex etiology and strong genetic predisposition. A number of investigations support the possible involvement of sigma non-opioid intracellular receptor 1 (SIGMAR1) in the pathophysiology of AD. We aimed to investigate the association between SIGMAR1 polymorphisms and late-onset AD, therefore we genotyped rs1799729 (GC-241-240TT) and rs1800866 (Q2P) in 322 Hungarian late-onset AD patients and 250 ethnically matched, elderly control individuals. The investigated polymorphisms were in nearly complete linkage disequilibrium resulting in the GC-Q and TT-P predominant haplotypes that were subjected to the statistical analyses. Our data demonstrates an association between the SIGMAR1 TT-P variant and the risk for developing AD (p=0.019), and a potential modest interaction effect (p=0.058) of the co-presence of the TT-P haplotype with apolipoprotein E4 allele on the risk for AD. Based on this mild significance, we could not fully support the hypothesis that TT-P haplotype in interaction with APOE E4 allele confers risk for developing AD. 相似文献
992.
Fiorillo C Moro F Brisca G Astrea G Nesti C Bálint Z Olschewski A Meschini MC Guelly C Auer-Grumbach M Battini R Pedemonte M Romano A Menchise V Biancheri R Santorelli FM Bruno C 《Neurogenetics》2012,13(3):195-203
Inherited disorders characterized by motor neuron loss and muscle weakness are genetically heterogeneous. The recent identification of mutations in the gene encoding transient receptor potential vanilloid 4 (TRPV4) in distal spinal muscular atrophy (dSMA) prompted us to screen for TRPV4 mutations in a small group of children with compatible phenotype. In a girl with dSMA and vocal cord paralysis, we detected a new variant (p.P97R) localized in the cytosolic N-terminus of the TRPV4 protein, upstream of the ankyrin-repeat domain, where the great majority of disease-associated mutations reside. In another child with congenital dSMA, in this case associated with bone abnormalities, we detected a previously reported mutation (p.R232C). Functional analysis of the novel p.P97R mutation in a heterologous system demonstrated a loss-of-function mechanism. Protein localization studies in muscle, skin, and cultured skin fibroblasts from both patients showed normal protein expression. No TRPV4 mutations were detected in four children with dSMA without bone or vocal cord involvement. Adding to the clinical and molecular heterogeneity of TRPV4-associated diseases, our results suggest that molecular testing of the TRPV4 gene is warranted in cases of congenital dSMA with bone abnormalities and vocal cord paralysis. 相似文献
993.
994.
Introduction
It has been shown that thrombomodulin (TM) considerably delays factor XIII (FXIII) activation and this effect is abrogated by Factor V Leiden (FVLeiden) mutation. The aim of the study was to explore the effect of TM on the cross-linking of α2-plasmin inhibitor (α2-PI) to fibrin in plasma samples of different FV genotypes and how this effect is related to the impaired fibrinolysis of FVLeiden carriers.Methods
In the plasma samples of fifteen individuals with different FV genotypes and in FV deficient plasma supplemented with wild type FV or FVLeiden coagulation was initiated by recombinant human tissue factor and phospholipids with or without recombinant human TM (rhTM). In the recovered clots the extent of α2-PI-fibrin cross-linking was evaluated by Western blotting and quantitative densitometry. The effect of rhTM on tissue plasminogen activator (tPA) induced clot lysis was measured by turbidimetric method.Results
rhTM significantly delayed the formation of α2-PI-fibrin α-chain heterodimers/oligomers in plasma samples containing wild type FV. This effect of rhTM was impaired in the presence of FVLeiden. rhTM delayed tPA-induced clot lysis and this effect of rhTM was more pronounced in plasma containing FVLeiden. When TAFIa was inhibited by potato carboxypeptidase inhibitor, rhTM accelerated clot lysis in the presence of wild type FV, which is explained by the delayed α2-PI-fibrin cross-linking. This effect of rhTM did not prevail in the presence of FVLeiden.Conclusion
FVLeiden abrogates the delaying effect of rhTM on α2-PI-fibrin cross-linking, which contributes to the impaired fibrinolysis observed in FVLeiden carriers. 相似文献995.
LC Martins NP Rocha KC Torres RR Dos Santos GS França EN de Moraes MA Mukhamedyarov AL Zefirov AA Rizvanov AP Kiyasov LB Vieira MM Guimarães ME Yalvaç AL Teixeira MA Bicalho Z Janka MA Romano-Silva A Palotás HJ Reis 《Journal of neuroimmunology》2012,251(1-2):73-79
Alzheimer's dementia (AD) is a degenerative brain disorder characterized mainly by cholinergic failure, but other neuro-transmitters are also deficient especially at late stages of the disease. Misfolded β-amyloid peptide has been identified as a causative agent, however inflammatory changes also play a pivotal role. Even though the most prominent pathology is seen in the cognitive functions, specific abnormalities of the central nervous system (CNS) are also reflected in the periphery, particularly in the immune responses of the body. The aim of this study was to characterize the dopaminergic and serotonergic systems in AD, which are also markedly disrupted along with the hallmark acetyl-choline dysfunction. Peripheral blood mono-nuclear cells (PBMCs) from demented patients were judged against comparison groups including individuals with late-onset depression (LOD), as well as non-demented and non-depressed subjects. Cellular sub-populations were evaluated by mono-clonal antibodies against various cell surface receptors: CD4/CD8 (T-lymphocytes), CD19 (B-lymphocytes), CD14 (monocytes), and CD56 (natural-killer (NK)-cells). The expressions of dopamine D(3) and D(4), as well as serotonin 5-HT(1A), 5-HT(2A), 5-HT(2B) and 5-HT(2C) were also assessed. There were no significant differences among the study groups with respect to the frequency of the cellular sub-types, however a unique profound increase in 5-HT(2C) receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT(2C), as well as the NK-cell cyto-toxicity, has been linked with cognitive derangement in dementia. These changes not only corroborate the existence of bi-directional communication between the immune system and the CNS, but also elucidate the role of inflammatory activity in AD pathology, and may serve as potential biomarkers for less invasive and early diagnostic purposes as well. 相似文献
996.
997.
Kamson DO Illés Z Aradi M Orsi G Perlaki G Leél-?ssy E Erdélyi-Botor S Pótó L Trauninger A Pfund Z 《Journal of clinical neuroscience》2012,19(5):696-701
Migraine and multiple sclerosis (MS) can both cause white matter lesions that appear similar on conventional MRI. This study aimed to compare these abnormalities, and to find anatomical biomarkers specific for migraine. Supratentorial white matter hyperintensities (WMH) of 17 migraineurs and 15 patients with MS were counted, volumetrically analyzed, and their lobar distribution assessed on fluid-attenuated inversion recovery MRI. We found that migraine WMH affected mainly the deep white matter and subcortical U-fibers, belonged to the anterior circulation, appeared more frequently in the frontal and parietal lobes, showed no difference in average size between lobes, and were smaller and fewer than in MS. Most of the MS WMH were in the frontal lobe and were the smallest average size, while the fewest WMH with the largest size were in the occipital lobe. The pattern of supratentorial WMH appearance differs between the two groups; however, accurate differential diagnosis of WMH by conventional MRI is probably not possible in individual patients. 相似文献
998.
Mechanisms controlling the guidance of thalamocortical axons through the embryonic forebrain 总被引:1,自引:0,他引:1
Molnár Z Garel S López-Bendito G Maness P Price DJ 《The European journal of neuroscience》2012,35(10):1573-1585
Thalamocortical axons must cross a complex cellular terrain through the developing forebrain, and this terrain has to be understood for us to learn how thalamocortical axons reach their destinations. Selective fasciculation, guidepost cells and various diencephalic and telencephalic gradients have been implicated in thalamocortical guidance. As our understanding of the relevant forebrain patterns has increased, so has our knowledge of the guidance mechanisms. Our aim here is to review recent observations of cellular and molecular mechanisms related to: the growth of thalamofugal projections to the ventral telencephalon, thalamic axon avoidance of the hypothalamus and extension into the telencephalon to form the internal capsule, the crossing of the pallial-subpallial boundary, and the growth towards the cerebral cortex. We shall review current theories for the explanation of the maintenance and alteration of topographic order in the thalamocortical projections to the cortex. It is now increasingly clear that several mechanisms are involved at different stages of thalamocortical development, and each contributes substantially to the eventual outcome. Revealing the molecular and cellular mechanisms can help to link specific genes to details of actual developmental mechanisms. 相似文献
999.
Busse S Bernstein HG Busse M Bielau H Brisch R Mawrin C Müller S Sarnyai Z Gos T Bogerts B Steiner J 《European archives of psychiatry and clinical neuroscience》2012,262(5):365-374
Protein expression of VGF (nonacronymic) is induced by nerve/brain-derived growth factor, neurotrophin 3, and insulin. VGF is synthesized by neurons in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. After enzymatic processing, smaller VGF-derived peptides are secreted into the cerebrospinal fluid (CSF) or blood. These peptides play important roles by improving synaptic plasticity, neurogenesis, and energy homeostasis, which are impaired in schizophrenia. Based on previous observations of neuroendocrine and hypothalamic deficits in schizophrenia and to determine whether increased levels of the VGF fragment 23-62 in CSF, which have been described in a recent study, were related to changes in hypothalamic VGF expression, an immunohistochemical study was performed in 20 patients with schizophrenia and 19 matched control subjects. N- (D-20) and C-terminal (R-15) VGF antibodies yielded similar results and immunolabeled a vast majority of PVN and SON neurons. Additionally, D20-VGF immunohistochemistry revealed immunostained fibers in the pituitary stalk and neurohypophysis that ended at vessel walls, suggesting axonal transport and VGF secretion. The cell density of D20-VGF-immunoreactive neurons was reduced in the left PVN (P = 0.002) and SON (P = 0.008) of patients with schizophrenia. This study provides the first evidence for diminished hypothalamic VGF levels in schizophrenia, which might suggest increased protein secretion. Our finding was particularly significant in subjects without metabolic syndrome (patients with a body mass index ≤28.7 kg/m(2)). In conclusion, apart from beneficial effects on synaptic plasticity and neurogenesis, VGF may be linked to schizophrenia-related alterations in energy homeostasis. 相似文献
1000.
Rocha NP Teixeira AL Coelho FM Caramelli P Guimarães HC Barbosa IG da Silva TA Mukhamedyarov MA Zefirov AL Rizvanov AA Kiyasov AP Vieira LB Janka Z Palotás A Reis HJ 《Molecular and cellular neurosciences》2012,49(1):77-84