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41.
Anthony J. Bonito Costica Aloman M. Isabel Fiel Nichole M. Danzl Sungwon Cha Erica G. Weinstein Seihwan Jeong Yongwon Choi Matthew C. Walsh Konstantina Alexandropoulos 《The Journal of clinical investigation》2013,123(8):3510-3524
TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate T cell tolerance by ectopically expressing self-antigens and eliminating autoreactive T cells in the thymus. Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expression in murine thymic epithelial cells (Traf6ΔTEC mice) showed a surprisingly narrow spectrum of autoimmunity affecting the liver. The liver inflammation in Traf6ΔTEC mice exhibited all the histological and immunological characteristics of human autoimmune hepatitis (AIH). The role of T cells in AIH establishment was supported by intrahepatic T cell population changes and AIH development after transfer of liver T cells into immunodeficient mice. Despite a 50% reduction in natural Treg thymic output, peripheral tolerance in Traf6ΔTEC mice was normal, whereas compensatory T regulatory mechanisms were evident in the liver of these animals. These data indicate that mTECs exert a cell-autonomous role in central T cell tolerance and organ-specific autoimmunity, but play a redundant role in peripheral tolerance. These findings also demonstrate that Traf6ΔTEC mice are a relevant model with which to study the pathophysiology of AIH, as well as autoantigen-specific T cell responses and regulatory mechanisms underlying this disease. 相似文献
42.
A Novel Advance Directives Course Provides a Transformative Learning Experience for Medical Students
Paul S. Mueller Scott C. Litin C. Christopher Hook Edward T. Creagan Stephen S. Cha Thomas J. Beckman 《Teaching and learning in medicine》2013,25(2):137-141
Background: Concept maps can assist learning by integrating new information with existing cognitive structure to facilitate meaningful understanding. The benefits of testable concept maps to illustrate cause-and-effect sequences in the pathogenesis of disease have not yet been determined. Purpose: A controlled trial was employed to evaluate the learning benefits of testable pathogenesis maps. Methods: Consecutive cohorts of junior medical students allocated to control and study groups participated in case-based pathology practical classes. Online testable pathogenesis maps were integrated into classes for the study group. An online quiz and questionnaire were used to evaluate outcomes. Results: The study group scored significantly higher on the quiz ( p= .014), including significantly better performance in topics covered by pathogenesis maps ( p= .049). The study group's questionnaire responses regarding pathogenesis maps were overwhelmingly positive. Conclusions: Testable pathogenesis maps significantly improved medical students’ understanding of the pathogenesis of disease. Wider use of such maps should be explored. 相似文献
43.
We have shown previously that electrical stimulation of the motor cortex reduces spontaneous painlike behaviors in animals with spinal cord injury (SCI). Because SCI pain behaviors are associated with abnormal inhibition in the inhibitory nucleus zona incerta (ZI) and because inactivation of the ZI blocks motor cortex stimulation (MCS) effects, we hypothesized that the antinociceptive effects of MCS are due to enhanced inhibitory inputs from ZI to the posterior thalamus (Po)—an area heavily implicated in nociceptive processing. To test this hypothesis, we used a rodent model of SCI pain and performed in vivo extracellular electrophysiological recordings in single well-isolated neurons in anesthetized rats. We recorded spontaneous activity in ZI and Po from 48 rats before, during, and after MCS (50 μA, 50 Hz; 300-ms pulses). We found that MCS enhanced spontaneous activity in 35% of ZI neurons and suppressed spontaneous activity in 58% of Po neurons. The majority of MCS-enhanced ZI neurons (81%) were located in the ventrorateral subdivision of ZI—the area containing Po-projecting ZI neurons. In addition, we found that inactivation of ZI using muscimol (GABAA receptor agonist) blocked the effects of MCS in 73% of Po neurons. Although we cannot eliminate the possibility that muscimol spread to areas adjacent to ZI, these findings support our hypothesis and suggest that MCS produces antinociception by activating the incertothalamic pathway.PerspectiveThis article describes a novel brain circuit that can be manipulated, in rats, to produce antinociception. These results have the potential to significantly impact the standard of care currently in place for the treatment of patients with intractable pain. 相似文献
44.
Cha SH Wolfgang M Tokutake Y Chohnan S Lane MD 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(44):16871-16875
The American diet, especially that of adolescents, contains highly palatable foods of high-energy content and large amounts of high-fructose sweeteners. These factors are believed to contribute to the obesity epidemic and insulin resistance. Previous investigations revealed that the central metabolism of glucose suppresses food intake mediated by the hypothalamic AMP-kinase/malonyl–CoA signaling system. Unlike glucose, centrally administered fructose increases food intake. Evidence presented herein indicates that the more rapid initial steps of central fructose metabolism deplete hypothalamic ATP level, whereas the slower regulated steps of glucose metabolism elevate hypothalamic ATP level. Consistent with effects on the [ATP]/[AMP] ratio, fructose increases phosphorylation/activation of hypothalamic AMP kinase causing phosphorylation/inactivation of acetyl–CoA carboxylase, whereas glucose has the inverse effects. The changes provoked by central fructose administration reduce hypothalamic malonyl–CoA level and thereby increase food intake. These findings explain the paradoxical fructose effect on food intake and lend credence to the malonyl–CoA hypothesis. 相似文献
45.
Effect of Granulocyte Colony-Stimulating Factor on Chemotherapeutic Activity of Cytosine Arabinoside in Acute Leukemic Cell Lines 总被引:1,自引:0,他引:1
Recent studies have shown the presence of receptors for granulocyte colony-stimulating factor (G-CSF) on lymphoid leukemic cells. To determine the effect of G-CSF on chemotherapeutic activity of cytosine arabinoside (Ara-C) on lymphoid as well as myeloid leukemic cells, we evaluated cell counts, apoptosis, and growth inhibition in HL-60, KG-1, Molt-4, Jijoye, and CCRF-CEM cell lines after incubation with Ara-C (0.1 and 1 micromol/L) and/or 5 ng/mL G-CSE G-CSF potentiated the effect of Ara-C on 2 of 3 lymphoid leukemic cell lines (Molt-4 and Jijoye), whereas it decreased the apoptosis and the effect of Ara-C on myeloid cell lines (HL-60 and KG-1). 相似文献
46.
Kwon HS Cho JH Kim HS Lee JH Song BR Oh JA Han JH Kim HS Cha BY Lee KW Son HY Kang SK Lee WC Yoon KH 《Diabetes research and clinical practice》2004,66(Z1):S133-S137
We developed a blood glucose management system using the Internet and short message service (SMS) which can lessen the social economic burden and materialize an individualized diabetes mellitus management. A total of 185 diabetic patients participated in this study and their mean age was 42.4 years old (8-79 year-old). Participants sent their self-measured blood glucose levels, medication and its dosages, amount of meal, and degree of exercise to their health providers in this specialized web-based diabetes management system for 3 months. The health providers consisting of endocrinology specialists, dietitians, and nurses sent recommendations for individualized diabetes management according to the data on the web. Laboratory tests including lipid profiles and glycated hemoglobin (HbA1c), and a survey of satisfaction about this system were performed before and after the study period. The mean HbA1c improved from 7.5 +/- 1.5 to 7.0 +/- 1.1% after using the management program (P = 0.003). The mean serum triglyceride and HDL-cholesterol levels turned for the better also. HbA1c improved from 8.4 +/- 1.2 to 7.5 +/- 1.0% after applying this program to patients with the HbA1c of 7% or higher at baseline (P = 0.010). We propose this web-based diabetic patient management system as a new tool for communication between health care providers and patients. 相似文献
47.
48.
Although gastrointestinal diseases are reported at various times throughout the year, some particular seasons are associated with a higher incidence of these diseases. This study aimed to identify the seasonal variations of peptic ulcer (PU), peptic ulcer bleeding (PUB), and acute pancreatitis (AP) in South Korea.We conducted a retrospective, observational cohort study of all subjects aged >18 years between 2012 and 2016 using the Health Insurance Review and Assessment-National Patient Samples database, previously converted to the standardized Observational Medical Outcomes Partnership-Common Data Model. We assessed the overall seasonal variations of PU, PUB, and AP and further analyzed seasonal variations according to age and sex subgroups.In total, 14,626 patients with PU, 3575 with PUB, and 9023 with AP were analyzed for 5 years. A clear seasonal variation was noted in PU, with the highest incidence rate during winter, the second highest during spring, the third highest during summer, and the lowest incidence during autumn for 5 years (P < .001). PUB also showed significant seasonal fluctuations, with winter peak for 4 years, except 1 year, which had a spring peak (P < .001). However, AP showed no clear seasonal variations (P = .090). No significant differences in the seasonal variation of PU, PUB, and AP were observed according to sex and age subgroups (<60 years vs ≥60 years).Seasonal variation of PU and PUB should be considered when determining allocation of available health care resources. 相似文献
49.
Lee Seulkee Kang Seonyoung Eun Yeonghee Kim Hyungjin Lee Jaejoon Koh Eun-Mi Kim Duk-Kyung Cha Hoon-Suk 《Clinical rheumatology》2022,41(6):1769-1777
Clinical Rheumatology - To describe the clinical characteristics and radiographic outcomes of vascular Behçet’s disease (BD) involving the aorta or its major branches. This retrospective... 相似文献