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101.
Emilie Da Costa Branquinho Guillaume Becker Cédric Bouteiller Ludovic Jean Pierre-Yves Renard Luc Zimmer 《Nuclear medicine and biology》2013,40(4):554-560
IntroductionDeveloping positron emission tomography (PET) radiotracers for non-invasive study of the cholinergic system is crucial to the understanding of neurodegenerative diseases. Although several acetylcholinesterase (AChE) PET tracers radiolabeled with carbon-11 exist, no fluorinated radiotracer is currently used in clinical imaging studies. The purpose of the present study is to describe the first fluorinated PET radiotracer for this brain enzyme.MethodsThree structural analogs of huprine, a specific AChE inhibitor presenting high affinity towards AChE in vitro, were synthesized and labeled with fluorine-18 via a mesylate/fluoro-nucleophilic aliphatic substitution: ([18 F]-FHUa, [18 F]-FHUb and [18 F]-FHUc). Initial biological evaluation included in vitro autoradiography in rat with competition with an AChE inhibitor at different concentrations, and microPET-scan on anesthetized rats. In vivo PET studies in anesthetized cat focused on [18 F]-FHUa.Results and ConclusionsAlthough radiosynthesis of these huprine analogs was straightforward, they showed poor brain penetration potential, partially reversed after pharmacological inhibition of P-glycoprotein. These results indicated that current huprine analogs are not suitable for PET mapping of brain AChE receptors, but require physicochemical modulation in order to increase brain penetration. 相似文献
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Pirus Ghadjar Wieslawa Blank-Liss Mathew Simcock Ivan Hegyi Karl T. Beer Holger Moch Daniel M. Aebersold Yitzhak Zimmer 《Clinical & experimental metastasis》2009,26(7):809-815
We investigated if the MET-activating point mutation Y1253D influences clinical outcomes in patients with advanced squamous cell carcinoma of the head
and neck (HNSCC). The study population consisted of 152 HNSCC patients treated by hyperfractionated radiotherapy alone or
concomitant with chemotherapy between September 1994 and July 2000. Tumors were screened for the presence of the MET-activating point mutation Y1253D. Seventy-eight patients (51%) received radiotherapy alone, 74 patients (49%) underwent radiotherapy
concomitant with chemotherapy. Median patient age was 54 years and median follow-up was 5.5 years. Distant metastasis-free
survival, local relapse-free survival and overall survival were compared with MET Y1253D status. During follow-up, 29 (19%) patients developed distant metastasis. MET Y1253D was detected in tumors of 21 out of 152 patients (14%). Distant metastasis-free survival (P = 0.008) was associated with MET Y1253D. In a multivariate Cox regression model, adjusted for T-category, only presence of MET Y1253D was associated with decreased distant metastasis-free survival: hazard ratio = 2.5 (95% confidence interval: 1.1,
5.8). The observed association between MET Y1253D-activating point mutation and decreased distant metastasis-free survival in advanced HNSCC suggests that MET may be a potential target for specific treatment interventions. 相似文献
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Dr. P. Zimmer 《Der Diabetologe》2011,7(1):27-30
The lack of endogenous insulin secretion in type 1 diabetes can cause dangerous hypo- and hyperglycemia during exercise in patients with type 1 diabetes. However, because of the increasing prevalence of obesity and lifestyle diseases, the beneficial effects of regular exercise clearly outweigh the dangers of exercising with type 1 diabetes. However, intensified training/education on metabolic regulation during exercise is necessary from the perspective of preventative medicine to be able to benefit fully from its effects. 相似文献
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The identification of tumor initiating cells or tumor stem cells capable of self-renewal has changed our fundamental view on tumorigenesis and tumor progression. A hierarchical order of different aggressive cell types derived from a small population of brain tumor stem cells is the basis for the heterogeneity in malignant gliomas. The glioma stem cells are extremely resistant to chemotherapy and radiotherapy they survive adjuvant cancer therapy and are the basis for recurrent tumor growth and clinical relapse. Therefore, modern therapies should be targeted against this cell type. It is a major goal to identify brain tumor stem cell markers for imaging and to enhance neuropathological diagnostics. 相似文献
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A cross-sectional transvaginal ultrasound study was conducted in 137 normal pregnancies with gestational ages ranging from 5-12 weeks. Several biometric measurements were obtained throughout pregnancy, including the three diameters of the gestational sac, the crown-rump length, and the yolk sac. In addition, the appearance of the embryo heartbeat and embryo body movements were evaluated. Linear relationships were found between the mean gestational sac diameters and gestational age (r = 0.911; P less than .00001) and between mean gestational sac growth and crown-rump length growth (r = 0.926; P less than .0001). A gestational sac could be identified at 5 weeks' gestation; embryo heartbeat was imaged when the mean gestational sac diameter measured 2 cm, and embryo body movements could be seen when the mean gestational sac diameter reached 3 cm. In the present study, embryo heartbeat was identifiable after 6 weeks and 4 days with a sensitivity of 100%, specificity of 93.1%, positive predictive value of 96.9%, and negative predictive value of 100%. The embryo body movements, which were absent before 7 weeks' gestation, were observed after 8 weeks' gestation with a sensitivity of 100%, specificity of 92.8%, positive predictive value of 94.3%, and negative predictive value of 100%. With identification by transvaginal sonographic evaluation, the following can serve as markers of normal embryo growth: a mean gestational sac diameter greater than 2 cm in the presence of the embryo heartbeat, or a mean sac diameter measurement greater than 3 cm in the presence of embryo movement. 相似文献
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