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31.
Experimental methods of ethanol administration 总被引:15,自引:0,他引:15
Techniques are reviewed for the experimental feeding of alcohol, including a liquid diet procedure invented 25 years ago. This technique results in much higher ethanol intake than with other approaches. As a consequence, various complications observed in alcoholics can be reproduced in animal models. These include fatty liver, hyperlipemia, various metabolic and endocrine disorders, tolerance to ethanol and other drugs, physical dependence and withdrawal and, in the baboon, liver fibrosis and cirrhosis. Variations of the liquid diet formulation are compared, and adequacy of nutrition in terms of minerals, vitamins, lipotropes, carbohydrates and proteins is discussed. The importance of selecting proper controls is emphasized. The respective advantages of three standardized basic rat formulas are reviewed: (i) an all-purpose (35% fat) diet, comparable to the diet previously referred to as the "Lieber-DeCarli formula" and suitable for most experimental applications, particularly those intended to mimic the clinical situation in which the various effects of alcohol occur in the setting of hepatic changes characterized by a fatty liver; (ii) a low-fat diet comparable in all respects to the preceding diet but with a lower fat content, intended to minimize the hepatic changes, and (iii) a high-protein formula particularly useful in those circumstances in which an oversupply of dietary protein might be recommended (i.e. pregnancy). Variations of this technique, including continuous intragastric infusion, are also discussed. It is concluded that, for most experimental studies of chronic alcohol consumption, the liquid diet technique provides one of the most efficient tools to study the effects of ethanol under controlled nutritional conditions because it allows for alcohol consumption of clinical relevance and offers flexibility to adjust to special experimental or physiologic needs by allowing for various substitutions required for a particular experimental design, including changes in lipids, proteins or other dietary constituents. The technique also facilitates the comparison with controls by simplifying the pair feeding and is the best procedure available for the study of the toxic effects of alcohol and their interactions with deficiency or excess of various nutrients. 相似文献
32.
To determine how choline supplementation affects the liver and whether it can protect against ethanol-induced liver injury, baboons were fed either normal or choline-supplemented diets, each with or without ethanol. Eighteen baboons were pair-fed for 3 to 4 years liquid diets with 50% of total energy as ethanol or isocaloric carbohydrate; ten animals were given our regular diets, whereas in eight the choline content was increased 5-fold. Six additional animals were fed individually with the control diets (with or without additional choline). With both ethanol-containing diets, ethanol intake was comparable and resulted in hepatic steatosis and striking mitochondrial lesions, with increases in serum bilirubin and SGOT, SGPT and glutamate dehydrogenase activities. In addition, of the five animals fed alcohol with the regular diet, one progressed to incomplete cirrhosis and two others developed perivenular and associated perisinusoidal fibrosis. Similarly, in the four baboons fed alcohol with choline supplementation, incomplete cirrhosis developed in one and perivenular fibrosis in two. Collagen deposition was demonstrated by immunoperoxidase with a specific antibody against procollagen Type III. These animals also displayed proliferation of myofibroblasts in the perivenular area and transformation of fat-storing cells to transitional cells in the perisinusoidal space, with associated enhanced collagen fiber deposition. Thus, in baboons, choline supplementation failed to prevent alcohol-induced steatosis and fibrosis. All parameters remained normal in the eight baboons fed the regular control diet. However, in the choline-supplemented controls, serum bilirubin, SGOT and glutamate dehydrogenase activities increased moderately and serum albumin decreased. Occasional fat droplets appeared in hepatocytes with mitochondrial changes (enlargement and alterations of the cristae) and an abundance of "myelin" figures in the cytoplasm, indicating that choline supplementation exerts moderate hepatotoxicity. 相似文献
33.
34.
Allan L Klein Susan E Jasper William E Katz Joseph F Malouf Linda A Pape Marcus F Stoddard Carolyn Apperson-Hansen Elizabeth A Lieber 《European heart journal》2006,27(23):2858-2865
AIMS: To compare the feasibility and safety of transoesophageal echocardiograpy-guided cardioversion (CV) with enoxaparin and unfractionated heparin (UFH) in patients with atrial fibrillation (AF). METHODS AND RESULTS: The Assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II pilot trial compared the safety and efficacy of enoxaparin with UFH in 155 patients with AF who were scheduled for transoesophageal echocardiography (TEE)-guided CV. Safety outcomes over a 5-week period were ischaemic stroke, major or minor bleeding, and death. Efficacy outcomes were length of stay (LOS) and return to normal sinus rhythm (NSR). Of the 76 patients assigned to the enoxaparin group, 72 (94.7%) had a transoesophageal echocardiogram and 63 (82.9%) had early CV, of which 59 (93.7%) were successful. Of the 79 UFH patients, 66 (83.5%) had a transoesophageal echocardiogram and 58 (73.4%) had early CV, of which 54 (98.2%) were successful. There were no significant differences in embolic events, bleeding, or deaths between groups. The enoxaparin group had shorter median LOS compared with the UFH group [3(2-4) vs. 4(3-5)] days; P<0.0001). There was also more NSR at 5 weeks in the enoxaparin group (76 vs. 57%; P=0.013). CONCLUSION: In the ACUTE II trial, there were no differences in safety outcomes between the two strategies. However, the enoxaparin group had a shorter LOS. Thus, the TEE-guided enoxaparin strategy may be considered a safe and effective alternative strategy for AF. The shorter LOS may translate to lower costs using the enoxaparin TEE-guided approach. 相似文献
35.
36.
Six human hematopoetic cell lines were successfully heterotransplanted into athymic (nude) and asplenic-athymic (lasat) neonatal mice. The tumors arising from leukemia and lymphoma cells could then be serially transplanted into adult nude mice. Seven days after the fourth serial mouse passage, each mouse was treated with goat immune gamma globulin against K-562 cells. One control group was treated similarly, but with nonimmune (normal) gamma globulin, while another control group was not treated. The goat gamma globulin was not toxic for nude and lasat mice, and the immune, but not the normal, gamma globulin suppressed local subcutaneous growth of myelosarcomas, lymphosarcomas, and Burkitt lymphoma cells. On the other hand, the growth of lung, breast, and prostatic carcinomas and a melanoma of human origin were not altered by the immune gamma globulin. Since suppression of cell growth occurred equally well in decomplemented mice, a complement-mediated cytotoxicity apparently cannot be considered as responsible for the abrogation. The Fab fragment of the immunoglobulin did not suppress the growth of the myelosarcomas. We conclude that antibody suppression of the in vivo proliferation was specific for malignant hematopoietic cells and that the Fc portion of IgG is necessary for in vivo cytolysis of leukemia cells. The most probable mechanisms are direct antibody cytolysis and antibody-dependent macrophage-mediated cytotoxicity. 相似文献
37.
38.
Srichai MB Schvartzman PR Sturm B Kasper JM Lieber ML White RD 《American heart journal》2004,148(2):342-348
Background
Hyper-enhancement on delayed-enhancement magnetic resonance imaging (DE-MRI) is a marker of irreversible myocardial injury. Both reversible and irreversible ischemically injured regions of myocardium develop reductions in systolic function compared with unaffected regions. This study evaluated whether there is a relationship between myocardial hyper-enhancement from remote scarring on DE-MRI and the degree of myocardial circumferential shortening (%CS) as determined with dynamic MRI tissue tagging (TAG-MRI) in the setting of chronic ischemic heart disease (CIHD).Methods
Thirty-five patients with CIHD and 8 control patients underwent nonstress, resting DE-MRI and TAG-MRI. A total of 168 CIHD and 96 control segments from the basal- and middle-thirds of the left ventricle (LV) were selected to achieve a balanced test set. With a 16-segment model, segmental myocardial scarring was graded on the basis of the amount of hyper-enhancement on DE-MRI. With TAG-MRI images, segmental %CS was calculated.Results
Patients with CIHD had lower LV ejection fraction compared with the control patients (28% vs 67%). The %CS of normal segments was notably different from %CS of CIHD segments, regardless of the presence or absence of myocardial hyper-enhancement on DE-MRI. Among the CIHD segments, however, %CS correlated inversely with the amount of myocardial hyper-enhancement from scarring (P <.0001, r = −0.38).Conclusions
On cardiac MRI for CIHD, myocardial hyper-enhancement correlates inversely with %CS, supporting the direct relationship between the amount of remote myocardial scarring determined with nonstress DE-MRI and baseline resting functional impairment. 相似文献39.
Lieber CS Weiss DG Groszmann R Paronetto F Schenker S;Veterans Affairs Cooperative Study Group 《Alcoholism, clinical and experimental research》2003,27(11):1757-1764
BACKGROUND: This multicenter prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the effectiveness of polyenylphosphatidylcholine against the progression of liver fibrosis toward cirrhosis in alcoholics. Seven hundred eighty-nine alcoholics with an average intake of 16 drinks per day were enrolled. To control excessive drinking, patients were referred to a standard 12-step-based alcoholism treatment program, but most patients refused to attend. Accordingly, study follow-up procedures incorporated the essential features of the brief-intervention approach. An overall substantial and sustained reduction in drinking was observed. Hepatic histological and other findings are described in a companion article. METHODS: Patients were randomized to receive daily three tablets of either polyenylphosphatidylcholine or placebo. Monthly follow-up visits included an extensive session with a medical nurse along with brief visits with a study physician (hepatologist or gastroenterologist). A detailed physical examination occurred every 6 months. In addition, telephone consultations with the nurse were readily available. All patients had a liver biopsy before entry; a repeat biopsy was scheduled at 24 and 48 months. RESULTS: There was a striking decrease in average daily alcohol intake to approximately 2.5 drinks per day. This was sustained over the course of the trial, lasting from 2 to 6 years. The effect was similar both in early dropouts and long-term patients, i.e., those with a 24-month biopsy or beyond. CONCLUSIONS: In a treatment trial of alcoholic liver fibrosis, a striking reduction in alcohol consumption from 16 to 2.5 daily drinks was achieved with a brief-intervention approach, which consisted of a relative economy of therapeutic efforts that relied mainly on treatment sessions with a medical nurse accompanied by shorter reinforcing visits with a physician. This approach deserves generalization to address the heavy drinking problems commonly encountered in primary care and medical specialty practices. 相似文献
40.
Chander Sadasivan David J. Fiorella Henry H. Woo Baruch B. Lieber 《Annals of biomedical engineering》2013,41(7):1347-1365
Many factors that are either blood-, wall-, or hemodynamics-borne have been associated with the initiation, growth, and rupture of intracranial aneurysms. The distribution of cerebral aneurysms around the bifurcations of the circle of Willis has provided the impetus for numerous studies trying to link hemodynamic factors (flow impingement, pressure, and/or wall shear stress) to aneurysm pathophysiology. The focus of this review is to provide a broad overview of such hemodynamic associations as well as the subsumed aspects of vascular anatomy and wall structure. Hemodynamic factors seem to be correlated to the distribution of aneurysms on the intracranial arterial tree and complex, slow flow patterns seem to be associated with aneurysm growth and rupture. However, both the prevalence of aneurysms in the general population and the incidence of ruptures in the aneurysm population are extremely low. This suggests that hemodynamic factors and purely mechanical explanations by themselves may serve as necessary, but never as necessary and sufficient conditions of this disease’s causation. The ultimate cause is not yet known, but it is likely an additive or multiplicative effect of a handful of biochemical and biomechanical factors. 相似文献