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991.
FI Romero MJ Mart��nez-Calatrava O S��nchez-Pernaute O Gualillo R Largo G Herrero-Beaumont 《British journal of pharmacology》2010,161(5):1012-1022
BACKGROUND AND PURPOSE
Non-steroidal anti-inflammatory drugs improve inflammatory cachexia in several conditions. Thus, we have explored inhibition of cyclooxygenase-2 (COX-2) in an experimental model of rheumatoid cachexia in rabbits.EXPERIMENTAL APPROACH
Chronic arthritis was induced in immunized rabbits by repeated intra-articular injections of ovalbumin. To increase the degree of systemic inflammation and also to induce atherosclerotic lesions, the animals were fed a hyperlipidaemic diet (2% cholesterol and 6% peanut oil) and were given an endothelial injury of the femoral artery. Rabbits were randomized to receive the COX-2 inhibitor celecoxib (10 mg·kg−1·day−1) or no treatment. After 4 weeks, sera, peripheral mononuclear cells and vessel specimens were collected.KEY RESULTS
Inhibition of COX-2 by celecoxib modulated the systemic inflammatory response and increased total cholesterol and triglyceride levels. Celecoxib also minimized weight loss and prevented serum albumin fall. At a vascular level, celecoxib reduced COX-2 protein in the femoral arterial wall, but did not modify size or the macrophage infiltration of femoral lesions nor the percentage of rabbits with spontaneous aortic plaques.CONCLUSIONS AND IMPLICATIONS
Our animal model induced a severe inflammatory cachexia, comparable to that of persistently active rheumatoid arthritis. The inhibition of COX-2 by celecoxib improves this state, suggesting that COX products play an important role in its development, without affecting the development or the progression of vascular lesions. Overall, these results suggest that celecoxib might be considered as a new therapeutic tool for the treatment of rheumatoid cachexia. 相似文献992.
GT Whiteside JM Dwyer JE Harrison CE Beyer T Cummons L Manzino L Mark GH Johnston BW Strassle A Adedoyin P Lu MJ Piesla CM Pulicicchio JCL Erve BJ Platt ZA Hughes KE Rogers DC Deecher EJ Trybulski JD Kennedy P Zhang L Leventhal 《British journal of pharmacology》2010,160(5):1105-1118
Background and purpose:
Antidepressants, which raise the CNS concentrations of 5-HT and noradrenaline, are frequently used in the treatment of chronic pain; however, it is not known if increasing CNS noradrenaline levels alone is sufficient for efficacy, in part resulting from a lack of small molecules with sufficient selectivity.Experimental approach:
In this report, we present the in vitro pharmacological and in vivo pharmacokinetic and pharmacological properties of the novel, orally available and CNS penetrant inhibitor of the noradrenaline transporter (NET), WAY-318068 (1-[(1S,2R)-1-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)propyl]-7-fluoro-3,3-dimethyl-1,3-dihydro-2H-indol-2-one).Key results:
WAY-318068 is a potent and effective inhibitor of the NET with a Ki of 8.7 nM in a binding assay, and an IC50 of 6.8 nM in an assay of transporter function, without significant binding to the dopamine transporter. Furthermore, the compound has only weak activity at the 5-HT transporter, leading to a functional selectivity of greater than 2500-fold. It is orally bioavailable with substantial quantities of the compound found in the CNS after oral dosing. As measured by microdialysis in rats, the compound causes a robust and significant increase in cortical noradrenaline levels without affecting 5-HT. WAY-318068 was effective in models of acute, visceral, inflammatory, osteoarthritic, neuropathic, diabetic and bone cancer pain, as well as in traditional models of depression at doses that do not cause motor deficits.Conclusions and implications:
Collectively, the present results support the conclusion that selectively increasing CNS levels of noradrenaline is sufficient for efficacy in models of depression and pain. 相似文献993.
Mediastinal invasion by bronchogenic carcinoma: CT signs 总被引:3,自引:0,他引:3
994.
Musculoskeletal tumors: follow-up with MR imaging after treatment with surgery and radiation therapy 总被引:7,自引:0,他引:7
Magnetic resonance (MR) imaging was used as a follow-up technique in 60 patients who underwent surgery and/or radiation therapy for primary malignant musculoskeletal tumors. MR imaging was performed on a 1.5-T imager with T1- and T2-weighted imaging sequences; MR imaging findings were confirmed by means of posttreatment surgery and histologic analysis or follow-up for at least 1 year. If a low-signal-intensity lesion was seen on T2-weighted images in a patient who had undergone radiation therapy or surgery, the patient usually did not have active tumor (sensitivity, 96%). If a high-signal-intensity lesion was seen after a patient had undergone only surgery, the patient had active tumor (six of six such cases). In patients who had undergone only radiation therapy, however, the presence of a high-signal-intensity lesion may indicate either active tumor or radiation-induced inflammatory changes. Thus, in such cases, differential diagnosis of active tumor may be difficult, if not impossible, to make from MR images. 相似文献
995.
Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype 总被引:13,自引:8,他引:5
The CAMPATH-1 family of antibodies recognize an abundant glycoprotein expressed on virtually all human lymphocytes. All rat IgM and IgG antibodies of this specificity are lytic with human complement, but only IgG2b is active in antibody-dependent cell-mediated cytotoxicity (ADCC). We compared the ability of IgM, IgG2a, and IgG2b to deplete lymphocytes in vivo in two patients with prolymphocytic transformation of B-cell chronic lymphocytic leukemia (CLL). The IgM (CAMPATH-1M) produced transient depletion of blood lymphocytes with consumption of complement but had no effect on solid masses or bone marrow. Similar transient depletion of blood lymphocytes was noted with the IgG2a (YTH34.5). In contrast, the IgG2b (CAMPATH-1G) produced long-lasting depletion of lymphocytes from blood and marrow and improvement in splenomegaly but no detectable changes in complement levels. These differences probably reflect the importance of Fc receptor binding for effective clearance of target cells in vivo. We treated 16 more patients with a variety of lymphoid malignancies and noted consistent effects on blood lymphocytes, marrow infiltration, and splenomegaly. At this dose level, there was comparatively little improvement in affected lymph nodes or extranodal masses. Nevertheless, the in vivo lympholytic ability of CAMPATH-1G is very potent as compared with other monoclonal antibodies (MoAbs) and may have applications in therapy of lymphoid malignancies and as an immunosuppressive agent. 相似文献
996.
M. Reverte MJ Garcia-Barrado and J. Moratinos 《Fundamental & clinical pharmacology》1991,5(8):663-676
In conscious fasted rabbits, the iv infusion of salbutamol (3 micrograms/kg per min) and clonidine (2 micrograms/kg per min) induced a blood glucose increase amenable to blockade, respectively by ICI 118551 (1 micrograms/kg per min) and idazoxan (20 micrograms/kg per min). Amidephrine (10 micrograms/kg per min) and salbutamol mediated an increase in plasma lactate which was attenuated by prazosin (50 micrograms/kg, sc) and ICI 118551 respectively. Clonidine did not alter basal plasma lactate. The iv infusion of adrenaline (0.3 micrograms/kg per min) evoked an increase in plasma lactate more sensitive to blockade by ICI 118551 than by prazosin. ICI 118551 also shortened the hyperglycaemic response to adrenaline, 3-Mercaptopicolinic acid (25 mg/kg) reduced salbutamol- and adrenaline-mediated hyperglycaemia and increased at the same time the lactate/glucose ratio. Our data show that plasma lactate levels may be regulated by alpha 1- and beta 2-excitatory adrenoceptor stimulation. However, only the increase in blood lactate derived from beta 2-adrenergic stimulation seems to contribute to the overall catecholamine-mediated hyperglycaemia. 相似文献
997.
Appendicitis: efficacy of color Doppler sonography 总被引:8,自引:1,他引:7
998.
999.
1000.
Objectives: To review the definition of non-adherence, its clinical and economic impact and identify its role and impact in clinical practice.
Methods: A selective review of the literature as conducted of articles and literature known to the authors.
Results: There is a paucity of studies examining specifically treatment non-adherence and its consequences in bipolar disorder. Few studies have systematically examined ways in which treatment adherence can impact treatment and improve outcome.
Conclusion: Non-adherence is common in the management of bipolar disorder. Clinicians and Researchers alike need to remain alert and be aware of issues related to non-adherence – in particular suicide. Like other course-modifiers non-adherence has to be considered, sought and addressed, and this is perhaps best done by including psychoeducation in routine clinical care. 相似文献
Methods: A selective review of the literature as conducted of articles and literature known to the authors.
Results: There is a paucity of studies examining specifically treatment non-adherence and its consequences in bipolar disorder. Few studies have systematically examined ways in which treatment adherence can impact treatment and improve outcome.
Conclusion: Non-adherence is common in the management of bipolar disorder. Clinicians and Researchers alike need to remain alert and be aware of issues related to non-adherence – in particular suicide. Like other course-modifiers non-adherence has to be considered, sought and addressed, and this is perhaps best done by including psychoeducation in routine clinical care. 相似文献