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Besides the design freedom offered by additive manufacturing, another asset lies within its potential to accelerate product development processes by rapid fabrication of functional prototypes. The premise to fully exploit this benefit for lightweight design is the accurate structural response prediction prior to part production. However, the peculiar material behavior, characterized by anisotropy, thickness dependency and scatter, still constitutes a major challenge. Hence, a modeling approach for finite element analysis that accounts for this inhomogeneous behavior is developed by example of laser-sintered short-fiber-reinforced polyamide 12. Orthotropic and thickness-dependent Young’s moduli and Poisson’s ratios were determined via quasi-static tensile tests. Thereof, material models were generated and implemented in a property mapping routine for finite element models. Additionally, a framework for stochastic finite element analysis was set up for the consideration of scatter in material properties. For validation, thin-walled parts on sub-component level were fabricated and tested in quasi-static three-point bending experiments. Elastic parameters showed considerable anisotropy, thickness dependency and scatter. A comparison of the predicted forces with experimentally evaluated reaction forces disclosed substantially improved accuracy when utilizing the novel inhomogeneous approach instead of conventional homogeneous approaches. Furthermore, the variability observed in the structural response of loaded parts could be reproduced by the stochastic simulations. 相似文献
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《Brain stimulation》2021,14(4):927-937
BackgroundIncreases in the volume of the amygdala and hippocampus after electroconvulsive therapy (ECT) are among the most robust effects known to the brain-imaging field. Recent advances in the segmentation of substructures of these regions allow for novel insights on the relationship between brain structure and clinical outcomes of ECT.ObjectiveWe aimed to provide a comprehensive synthesis of evidence available on changes in brain structure after ECT, including recently published data on hippocampal subfields.MethodsA meta-analysis of published studies was carried out using random-effects models of standardized mean change of regional brain volumes measured with longitudinal magnetic resonance imaging of depressive patients before and after a series of ECT.ResultsData from 21 studies (543 depressed patients) were analysed, including 6 studies (118 patients) on hippocampal subfields. Meta-analyses could be carried out for seven brain regions for which data from at least three published studies was available. We observed increases in left and right hippocampi, amygdalae, cornua ammonis (CA) 1, CA 2/3, dentate gyri (DG) and subicula with standardized mean change scores ranging between 0.34 and 1.15. The model did not reveal significant volume increases in the caudate. Meta-regression indicated a negative relationship between the reported increases in the DG and relative symptom improvement (−0.27 (SE: 0.09) per 10%).ConclusionsECT is accompanied by significant volume increases in the bilateral hippocampus and amygdala that are not associated with treatment outcome. Among hippocampal subfields, the most robust volume increases after ECT were measured in the dentate gyrus. The indicated negative correlation of this effect with antidepressant efficacy warrants replication in data of individual patients. 相似文献
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IntroductionWe explored the potential clinical effects of angiotensin-II AT1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) in patients from the Parkinson's Progress Marker Initiative (PPMI) study database.MethodsWe included 423 newly diagnosed PD patients, free from antiparkinsonian treatment, from the PPMI. We compared the proportion of patients starting on l-DOPA during the first year of follow-up, and the changes in MDS-UPDRS total score and sub-scores during the first five follow-up years for patients exposed or not to ARBs or ACEIs.ResultsTreatment with ARBs did not affect the proportion of patients on l-DOPA during the first year (adjusted OR, 95% CI = 0.26, 0.03–2.18, N.S.) while reduced MDS-UPDRS total score (0.85, 0.76–0.95, p < 0.01). Patients treated with ACEIs experienced no changes in either measure.ConclusionsThese results show potential signals for a beneficial effect with ARBs. Further clinical trials are warranted. 相似文献
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Naveen Pemmaraju MD Jacqueline S. Garcia MD Andrew Perkins MBBS PhD Jason G. Harb PhD Andrew J. Souers PhD Michael E. Werner PhD Christopher M. Brown PhD Francesco Passamonti MD 《Cancer》2023,129(22):3535-3545
Myelofibrosis is a heterogeneous myeloproliferative neoplasm characterized by chronic inflammation, progressive bone marrow failure, and hepatosplenic extramedullary hematopoiesis. Treatments like Janus kinase inhibitor monotherapy (e.g., ruxolitinib) provide significant spleen and symptom relief but demonstrate limited ability to lead to a durable disease modification. There is an urgent unmet medical need for treatments with a novel mechanism of action that can modify the underlying pathophysiology and affect the disease course of myelofibrosis. This review highlights the role of B-cell lymphoma (BCL) protein BCL-extra large (BCL-XL) in disease pathogenesis and the potential role that navitoclax, a BCL-extra large/BCL-2 inhibitor, may have in myelofibrosis treatment. 相似文献
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Due to the fundamental progress in elucidating the molecular mechanisms of human diseases and the arrival of the post-genomic era, increasing numbers of therapeutic genes and cellular targets are available for gene therapy. Meanwhile, the most important challenge is to develop gene delivery vectors with high efficiency through target cell selectivity, in particular under in situ conditions. The most widely used vector system to transduce cells is based on adenovirus (Ad). Recent endeavors in the development of selective Ad vectors that target cells or tissues of interest and spare the alteration of all others have focused on the modification of the virus broad natural tropism. A popular way of Ad targeting is achieved by directing the vector towards distinct cellular receptors. Redirecting can be accomplished by linking custom-made peptides with specific affinity to cellular surface proteins via genetic integration, chemical coupling or bridging with dual-specific adapter molecules. Ideally, targeted vectors are incapable of entering cells via their native receptors. Such altered vectors offer new opportunities to delineate functional genomics in a natural environment and may enable efficient systemic therapeutic approaches. This review provides a summary of current state-of-the-art techniques to specifically target adenovirus-based gene delivery vectors. 相似文献
49.
In this paper we describe an efficient tool based on natural language processing for classifying the detail state of pulmonary embolism (PE) recorded in CT pulmonary angiography reports. The classification tasks include: PE present vs. absent, acute PE vs. others, central PE vs. others, and subsegmental PE vs. others. Statistical learning algorithms were trained with features extracted using the NLP tool and gold standard labels obtained via chart review from two radiologists. The areas under the receiver operating characteristic curves (AUC) for the four tasks were 0.998, 0.945, 0.987, and 0.986, respectively. We compared our classifiers with bag-of-words Naive Bayes classifiers, a standard text mining technology, which gave AUC 0.942, 0.765, 0.766, and 0.712, respectively. 相似文献
50.
Tara S Beattie Parinita Bhattacharjee Shajy Isac HL Mohan Milena Simic-Lawson BM Ramesh James F Blanchard Stephen Moses Charlotte H Watts Lori Heise 《Journal of the International AIDS Society》2015,18(1)