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1.
Tebuconazole is a systemic follicular fungicide known to cause diverse problems in non-target organisms namely associated to the pure active ingredient. As such, the objective of this work was to evaluate developmental changes induced by a tebuconazole commercial formulation to a non-target animal model. Zebrafish embryos at ± 2 h post-fertilization were exposed to tebuconazole wettable powder concentrations (0.05, 0.5 and 5 mg L-1) for 96 h with developmental toxicity assessed throughout the exposure period and biochemical parameters evaluated at the end of the exposure. Behavioural assessment (spatial exploration and response to stimuli) was conducted 24 h after the end of the exposure. While no developmental and physiological alterations were observed, exposure to tebuconazole resulted in an increased generation of reactive oxidative species at the 0.05 and 0.5 mg L-1 concentrations and a decreased GPx activity at the 0.5 mg L-1 concentration suggesting a potential protection mechanism. There was also a change in the avoidance-escape behaviour supporting an anxiolytic effect suggesting possible alterations in the central nervous system development demanding further studies.  相似文献   
2.
We propose a computational model to study the growth and spread of bacterial biofilms on interfaces, as well as the action of antibiotics on them. Bacterial membranes are represented by boundaries immersed in a fluid matrix and subject to interaction forces. Growth, division and death of bacterial cells follow dynamic energy budget rules, in response to variations in environmental concentrations of nutrients, toxicants and substances released by the cells. In this way, we create, destroy and enlarge boundaries, either spherical or rod-like. Appropriate forces represent details of the interaction between cells, and the interaction with the environment. We can investigate geometrical arrangements and the formation of porous structures. Numerical simulations illustrate the evolution of top views and diametral slices of small biofilm seeds, as well as the action of antibiotics. We show that cocktails of antibiotics targeting active and dormant cells can entirely eradicate a biofilm.  相似文献   
3.
Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function was consistently observed in association with either hEPCR (n = 15), hTBM (n = 4), or hEPCR.hTFPI (n = 11), but the loss of vascular barrier function in the xenograft and systemic inflammation in the recipient typically occurred within 24 h. Co-expression of hEPCR and hTBM (n = 11) and additionally blocking multiple pro-inflammatory innate and adaptive immune mechanisms was more consistently associated with survival >1 day, with one recipient surviving for 31 days. Combining targeted genetic modifications to the lung xenograft with selective innate and adaptive immune suppression enables prolonged initial life-supporting lung function and extends lung xenograft recipient survival, and illustrates residual barriers and candidate treatment strategies that may enable the clinical application of other organ xenografts.  相似文献   
4.
《Molecular therapy》2022,30(8):2856-2867
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5.
ObjectiveTo explore the protective effect and potential mechanisms of danshen root (Salvia miltiorrhiza Bge., S. miltiorrhiza) and its extracts for the treatment of diabetic nephropathy (DN).MethodsPreclinical studies of S. miltiorrhiza and its extracts on DN were systematically searched in nine databases. The primary outcomes were blood glucose, kidney function, proteinuria, and renal histopathology. The secondary outcomes included the related mechanisms. The methodological quality of animal studies was assessed based on the risk of bias tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) for animal studies. Meta-analysis was performed using R software (version 4.1.2).ResultsTwenty-nine animal experimental studies that met the eligibility criteria were included in this study. Compared to the control group, S. miltiorrhiza reduced the serum creatinine, blood urea nitrogen, 24-h urine protein, 24-h urine albumin, blood glucose, and kidney index (kidney weight/body weight), and alleviated renal pathological damage. In terms of the mechanism of action, compared to the control group, S. miltiorrhiza reduced the levels of transforming growth factor β1, collagen IV, malondialdehyde, tumor necrosis factor α, interleukin-6, and monocyte/macrophage (ED-1), and increased the levels of superoxide dismutase, glutathione peroxidase, nuclear factor E2–related factor 2, and heme oxygenase-1.ConclusionThe existing evidence shows that S. miltiorrhiza has beneficial effects on the animal model of DN, and its mechanism is mainly related to improving kidney fibrosis, oxidative stress, and inflammatory response.  相似文献   
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7.
BackgroundPulmonary tuberculosis is a highly prevalent disease in low-income countries; clinical prediction tools allow healthcare personnel to catalog patients with a higher risk of death in order to prioritize medical attention.MethodologyWe conducted a literature search on prognostic models aimed to predict mortality in patients diagnosed with pulmonary tuberculosis. We included prospective and retrospective studies where prognostic models predicting mortality were either developed or validated in patients diagnosed with pulmonary tuberculosis. Three reviewers independently assessed the quality of the included studies using the PROBAST tool (Prediction model study Risk of Bias Assessment Tool). A narrative review of the characteristics of each model was conducted.ResultsSix articles (n = 3553 patients) containing six prediction models were included in the review. Most studies (5 out of 6) were retrospective cohorts, only one study was a prospective case-control study. All the studies had a high risk of bias according to the PROBAST tool in the overall assessment. Regarding the applicability of the prediction models, three studies had a low concern of applicability, two high concern and one unclear concern. Five studies developed new prediction rules. In general, the presented models had a good discriminatory ability, with areas under the curve fluctuating between 0.65 up to 0.91.ConclusionNone of the prognostic models included in the review accurately predict mortality in patients with pulmonary tuberculosis, due to great heterogeneity in the population and a high risk of bias.  相似文献   
8.
《Diagnostic Histopathology》2022,28(11):493-500
After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.  相似文献   
9.
《Clinical breast cancer》2021,21(5):e497-e505
BackgroundDifferent clinicopathologic characteristics could contribute to inconsistent prognoses of small breast neoplasms (T1a/T1b). This study was done to conduct a retrospective analysis and establish a clinical prediction model to predict individual survival outcomes of patients with small carcinomas of the breast.Materials and MethodsBased on the Surveillance, Epidemiology, and End Results (SEER) database, eligible patients with small breast carcinomas were analyzed. Univariate analysis and multivariate analysis were performed to clarify the indicators of overall survival. Pooling risk factors enabled nomograms to be constructed and further predicted 3-year, 5-year, and 10-year survival of patients with small breast cancer. The model was internally validated for discrimination and calibration.ResultsA total of 17,543 patients with small breast neoplasms diagnosed between 2013 and 2016 were enrolled. Histologic grade, lymph node stage, estrogen receptor or progesterone receptor status, and molecular subtypes of breast cancer were regarded as the risk factors of prognosis in a Cox proportional hazards model (P < .05). A nomogram was constructed to give predictive accuracy toward individual survival rate of patients with small breast neoplasms.ConclusionsThis prognostic model provided a robust and effective method to predict the prognosis of patients with small breast cancer.  相似文献   
10.
Purpose/settingTo encourage clinical and financial efficiency, the Canadian province of Ontario initiated an integrated care program – Integrated Funding Models (IFMs) that required collaboration and coordination across acute and post-acute care sectors. This research shows how program implementers went beyond policy-makers’ original designs, to make integrated care sustainable for chronic diseases.MethodsForty-five interviews were conducted with program participants at three chronic disease programs, as well as with policymakers. Interviews were conducted over two phases; during early implementation in 2016, and as programs matured in 2018. Data were analyzed through a cultural constructivist lens to understand how participants shaped programs.FindingsParticipants desired greater accountability and control. Participants in the first program wanted localized control over decision-making. In the second, participants initiated greater control over financial uncertainty. In the third program, hospital participants sought greater control over community care. Participants across programs simultaneously wanted integrated care to be expanded holistically, spatially, and temporally for patients, extending the length of care, and expanding the spaces in which care was provided. Findings also suggest a gap between program implementers’ and policymakers’ conceptualizations of integrated care.ConclusionThis work shows how IFMs were reimagined in ways that transcended their original conceptualization as spatially and temporally delimited initiatives aimed at improving coordination and efficiency. It has practical implications for those facing sustainability challenges in other contexts.  相似文献   
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