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61.
62.
Biologic basis for interleukin-1 in disease 总被引:164,自引:6,他引:164
To understand the role of the proinflammatory cytokine interleukin-1 (IL-1) in disease, investigators have studied how production of the different members of the IL-1 family is controlled, the various biologic activities of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R) family, and the complexity of intracellular signaling. Mice deficient in IL-1Beta, IL-1Beta converting enzyme, and IL-1R type I have also been studied. Humans have been injected with IL- 1 (either IL-1alpha or IL-1beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1-specific receptor antagonist (IL-1Ra) has also been tested in clinical trials. The topics discussed in this review include production and activities of IL-1 and IL-1Ra molecules, the effects of IL-1 on gene expression, functions of cell-bound and soluble IL-1 receptors, the importance of the IL-1R accessory protein, newly discovered signal transduction pathways, naturally occurring cytokines limiting IL-1 production or activity, the effects of blocking cyclooxygenase and nitric oxide, and the outcomes of IL-1 and IL-1 Ra in human trials. Special attention is paid to IL-1beta converting enzyme and programmed cell death. The roles of IL-1 in hematopoiesis, leukemia, atherosclerosis, and growth of solid tumors are also discussed. This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references. At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease. 相似文献
63.
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Erythropoietic activity is known to be closely associated with marrow iron uptake. A modification of the standard measure of plasma iron turnover has been developed in which erythron transferrin uptake (ETU) rather than iron uptake has been calculated. The ETU has the advantage of providing a parameter of erythroid marrow activity independent of change produced by plasma iron and transferrin saturation. Measurements in 80 patients with anemia were compared to the normal value of 60 +/- 12 mumol/L whole blood/d. The mean ETU for ten patients with severe aplastic anemia and for six patients with pure red-cell aplasia were 12 +/- 8 and 12 +/- 11 mumol/L whole blood/d, respectively. In ten transfusion-dependent patients with renal failure under dialysis therapy, the mean value was 35 +/- 11, while ten other dialyzed patients who were transfusion independent had a mean ETU of 73 +/- 21 mumol/L whole blood/d. Sixteen patients with hemolytic anemia had an average ETU of 400 +/- 130, while 28 patients with ineffective erythropoiesis had a mean value of 474 +/- 147 mumol/L whole blood/d. While patients with hypoproliferative anemia showed no relation between the severity of anemia and ETU, those with hyperproliferative erythroid marrow showed increasing values as the anemia became more severe. Sequential measurements in patients with aplastic anemia under treatment and in thalassemic patients under transfusion therapy showed the value of this measurement in monitoring the effects of treatment on erythroid marrow activity. It is concluded that the measurement of ETU provides a more direct ferrokinetic evaluation of erythroid activity in anemic states. 相似文献
65.
The role of defective fibrinolysis caused by elevated activity of plasminogen activator inhibitor-1 (PAI-1) in promoting fibrin deposition in vivo has not been well established. The present study compared the efficacy of thrombin or ancrod, a venom-derived enzyme that clots fibrinogen, to induce fibrin formation in rabbits with elevated PAI-1 levels. One set of male New Zealand rabbits received intravenous endotoxin to increase endogenous PAI-1 activity followed by a 1-hour infusion of ancrod or thrombin; another set of normal rabbits received intravenous human recombinant PAI-1 (rPAI-1) during an infusion of ancrod or thrombin. Thirty minutes after the end of the infusion, renal fibrin deposition was assessed by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or thrombin alone did not develop renal thrombi. All endotoxin-treated rabbits developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n = 6). Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1 and ancrod and in only 1 of 6 receiving rPAI-1 and thrombin (P < .01). In vitro, thrombin but not ancrod was inactivated by normal rabbit plasma and by purified antithrombin III or thrombomodulin. The data indicate that elevated levels of PAI-1 promote fibrin deposition in rabbits infused with ancrod but not with thrombin. In endotoxin-treated rabbits, fibrin deposition that occurs with thrombin infusion may be caused by decreased inhibition of procoagulant activity and not increased PAI-1 activity. 相似文献
66.
Identification of T lymphocytes in human mixed hemopoietic colonies 总被引:11,自引:0,他引:11
The addition of a T-cell growth-promoting medium (PHA-TCM) to culture conditions that support growth of multi-lineage hemopoietic colonies enhances the proliferation of cells with lymphoid morphology within these colonies. These cells were identified as T lymphocytes by their ability to form rosettes with SRBC and their reaction with monoclonal antibodies (OKT3, OKT4) directed against T-cell-specific surface components. They continue to proliferate extensively under the influence of PHA-TCM after transfer of mixed colonies into liquid suspension culture. Supportive evidence for a common progenitor of myeloid and lymphoid cells within single mixed colonies is provided by Y-chromatin body analysis of E-rosette positive and negative cells in colonies grown in cocultures of male and female bone marrow cells. 相似文献
67.
Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis 总被引:1,自引:0,他引:1
The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable. 相似文献
68.
Chung T Martin CS Grella CE Winters KC Abrantes AM Brown SA 《Alcoholism, clinical and experimental research》2003,27(2):253-261
Knowledge of the clinical course in treated adolescents is fundamental to determining the influence of treatment on long-term functioning and the factors associated with change in the severity of alcohol problems over time. This symposium, held at the 2002 annual Research Society on Alcoholism meeting and organized by Tammy Chung and Christopher S. Martin, presented research on the course of alcohol-related problems in treated adolescents who were followed prospectively for 1 to 8 years. Presentations included (1) Alcohol use outcomes at 1 year among adolescents in the drug abuse treatment outcomes studies (DATOS-A), by Christine E. Grella; (2) Pathways and predictors of the course of adolescent alcohol problems across 1- and 3-year follow-ups, by Tammy Chung; (3) Young adult outcomes of an adolescent clinical sample at 5-year follow-up, by Ken C. Winters; and (4) Trajectories of alcohol involvement following addiction treatment through 8-year follow-up in adolescents, by Ana M. Abrantes, Denis M. McCarthy, Gregory A. Aarons, and Sandra A. Brown. Sandra A. Brown, discussant, commented on the presentations. Results from these studies indicate multiple pathways of change, distinguished by fluctuations in the chronicity and severity of alcohol problems. Across studies, most adolescents showed reductions in alcohol use and problems after treatment, with concurrent improvements in psychosocial functioning. Findings highlight the influence of other drug use on posttreatment patterns of alcohol involvement and the need to consider the effect of normative developmental transitions on the course of adolescent-onset substance use disorders. 相似文献
69.
Bryan D. Hayes Michael E. Winters Steve B. Rosenbaum Mohannad F. Allehyani Gary M. Vilke 《The Journal of emergency medicine》2018,54(4):571-575
Background
In 2010, the U.S. Food and Drug Administration (FDA) approved dabigatran as the first non-warfarin oral anticoagulant for use in the United States. At the time of FDA approval, there was no antidote or effective treatment for dabigatran-induced hemorrhage. In 2015, the FDA approved idarucizumab for the treatment of dabigatran-induced hemorrhage. The purpose of this clinical practice statement is to evaluate the role of select reversal agents in the management of patients with dabigatran-associated bleeding.Methods
A PubMed literature review was completed to identify studies that investigated the role of reversal agents in the management of emergency department patients with dabigatran-associated hemorrhage. Articles included were those published in the English language between January 2010 and January 2017, enrolled human subjects, and limited to the following types: randomized controlled trials, prospective trials, meta-analyses, and retrospective cohort studies. Review articles, case series, and case reports were not included in this review. All selected articles then underwent a structured review by the authors.Results
Six hundred fifty-two articles were identified in the search. After use of predetermined inclusion and exclusion criteria, six articles were selected for structured review.Conclusion
The clinical efficacy of activated prothrombin complex concentrates, idarucizumab, and recombinant factor VIIa remains unclear until further research is performed. Activated prothrombin complex concentrates, idarucizumab, and recombinant factor VIIa may be considered in patients with serious bleeding from dabigatran, after careful consideration of possible benefits and risks. 相似文献70.