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Adeola T Adeleye O Potts JL Faulkner M Oso A 《Journal of the National Medical Association》2001,93(7-8):282-287
Autosomal dominant polycystic kidney disease is one of the most common hereditary diseases, and frequently has well defined extrarenal manifestations. Very few cases of aortic aneurysms associated with this disorder are described in literature. We report a 42-year-old male with autosomal dominant polycystic kidney disease presenting with dissecting aneurysm of the thoracic aorta. 相似文献
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Peter Baltrus Junjun Xu Lilly Immergluck Anne Gaglioti Adeola Adesokan George Rust 《The Journal of asthma》2017,54(1):53-61
Objective: Disparities in asthma outcomes are well documented in the United States. Interventions to promote equity in asthma outcomes could target factors at the individual and community levels. The objective of this analysis was to understand the effect of individual (race, gender, age, and preventive inhaler use) and county-level factors (demographic, socioeconomic, health care, air-quality) on asthma emergency department (ED) visits among Medicaid-enrolled children. This was a retrospective cohort study of Medicaid-enrolled children with asthma in 29 states in 2009. Multilevel regression models of asthma ED visits were constructed utilizing individual-level variables (race, gender, age, and preventive inhaler use) from the Medicaid enrollment file and county-level variables reflecting population and health system characteristics from the Area Resource File (ARF). County-level measures of air quality were obtained from Environmental Protection Agency (EPA) data. Results: The primary modifiable risk factor at the individual level was found to be the ratio of long-term controller medications to total asthma medications. County-level factors accounted for roughly 6% of the variance in the asthma ED visit risk. Increasing county-level racial segregation (OR=1.04, 95% CI=1.01-1.08) was associated with increasing risk of asthma ED visits. Greater supply of pulmonary physicians at the county level (OR=0.81, 95% CI=0.68-0.97) was associated with a reduction in risk of asthma ED visits. Conclusions: At the patient care level, proper use of controller medications is the factor most amenable to intervention. There is also a societal imperative to address negative social determinants, such as residential segregation. 相似文献
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Kelly L Conrad Adeola R Davis Yuval Silberman Douglas J Sheffler Angela D Shields Sam A Saleh Namita Sen Heinrich JG Matthies Jonathan A Javitch Craig W Lindsley Danny G Winder 《Neuropsychopharmacology》2012,37(10):2253-2266
The alpha2 adrenergic receptor (α2-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward pathways, and produces an impairment of extinction of cocaine-conditioned place preference (cocaine-CPP) independent of α2-AR signaling. Recent studies show yohimbine-induced drug-seeking behavior is attenuated by orexin receptor 1 (OX1R) antagonists. Moreover, yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we investigated yohimbine-orexin interactions. Our results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR1) antagonists, but is (1) blocked by OxR antagonists and (2) absent in brain slices from orexin knockout mice. Although the actions of yohimbine were not mimicked by the norepinephrine transporter blocker reboxetine, they were by exogenously applied orexin A. We find that, as with yohimbine, orexin A depression of excitatory transmission in BNST is OX1R–dependent. Finally, we find these ex vivo effects are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction is blocked by a systemically administered OX1R antagonist. These data highlight a new mechanism for orexin on excitatory anxiety circuits and demonstrate that some of the actions of yohimbine may be directly dependent upon orexin signaling and independent of norepinephrine and CRF in the BNST. 相似文献
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Md. Shahidul Ahsan Manabu Yamazaki Satoshi Maruyama Takanori Kobayashi Hiroko Ida‐Yonemochi Mayumi Hasegawa Adeola Henry Ademola Jun Cheng Takashi Saku 《Journal of oral pathology & medicine》2011,40(7):552-559
J Oral Pathol Med (2011) 40 : 552–559 Objectives: The deposition of perlecan, a heparan sulfate proteoglycan, is enhanced within oral carcinoma in situ (CIS) foci, while it dynamically switches from CIS foci to the stromal space in squamous cell carcinoma (SCC). Because α‐dystroglycan and integrin β1 have been identified as two of the perlecan receptors, we wanted to determine their differential distributions before and after invasion of oral SCC. Methods: Eighty‐two surgical tissue specimens of oral SCC containing different precancerous stages were examined by immunohistochemistry for perlecan, α‐dystroglycan, integrin β1, and Ki‐67. In addition, α‐dystroglycan mRNA signals were localized by in situ hybridization. Results: In normal epithelia, α‐dystroglycan and integrin β1 were localized on the cell membrane of basal cells, while perlecan was faintly present in the intercellular spaces of parabasal cells. In epithelial dysplasia and CIS, α‐dystroglycan and perlecan were well co‐localized in the epithelial layer, especially in its lower half, and this co‐localization was mostly overlapped with Ki‐67‐positive (+) cell zones. However, in SCC, α‐dystroglycan was localized neither within carcinoma cell nests nor in the stroma, while perlecan disappeared from SCC foci but emerged in the stromal space, leaving integrin β1+ and Ki‐67+ cells only to the periphery of SCC foci. α‐Dystroglycan mRNA signals were basically identical to the α‐dystroglycan protein localizations. Conclusion: The findings suggest that α‐dystroglycan and integrin β1 act as perlecan receptors in oral precancerous lesions prior to invasion, and that the perlecan signals via the two different receptors function in cellular differentiation and proliferation of CIS cells, respectively. 相似文献
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This study details the separate analyses of binding specificity of HIV-1 integrase (IN) and viral B-DNA forms through ligand-receptor docking studies by means of a fast molecular docking method. The application of solvated electrostatics with the University of Houston Brownian Dynamics Program (UHBD) and configurational sampling by the Daughter of Turnip (DOT) docking program resulted in the computation of energies of more than 113 billion configurations for each ligand-receptor docking study, a procedure considered computationally intractable a few years ago. A specific binding pattern of viral DNA to the IN catalytic domain region has been predicted as a result of these calculations. In a representative docked configuration, we observe the 3'-hydroxyl of the conserved deoxyadenosine to be close to one of the two divalent metal ions that are necessary for catalysis. A superimposition of our energy-minimized docked complex on representative structures from a molecular dynamics (MD) simulation of a crystallographically resolved IN/inhibitor complex revealed an overlap of viral DNA with the inhibitor, indicating that the bound inhibitor might operate by blocking substrate binding. The DOT docking calculation also identified a second, adjacent DNA-binding site, which we believe is the nonspecific host DNA binding site. The binding pattern predicted by DOT complements previous electrostatics, MD simulation, photo-cross-linking, and mutagenesis studies and also provides a further refinement of the IN/viral DNA binding interaction as a basis for new structure-based design efforts. 相似文献
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Rationale Age of initial exposure to addictive substances is inversely proportional to risk of developing drug dependence. There is debate, however, as to whether intake at a young age causes dependency or whether young people who experiment with addictive substances are predisposed to dependency by other factors.Objectives We tested the relationship between cocaine exposure at two different ages in mice and the development of subsequent drug-seeking behavior to test for age-specific exposure effects.Methods We performed dose-response analysis of cocaine conditioned place preference (CPP) and locomotor activity in periadolescent and adult C57Bl/6J mice. In addition, we pretreated periadolescent and adult C57Bl/6J mice with cocaine or saline in the home cage or a drug-associated context, and then examined their behavior in a biased CPP procedure in adulthood.Results Dose-response relationships were similar between the two age groups. In the pretreatment experiments, we observed locomotor sensitization during the pretreatment in periadolescent but not adult mice. We also observed an enhanced aversion to the non-preferred side of the chamber in periadolescent mice compared to adult mice, which was alleviated by cocaine association with that side. Third, we observed that after further conditioning in adulthood, there were no pretreatment-specific effects.Conclusions Our results are consistent with a vulnerable brain hypothesis for responses to cocaine based on our findings that periadolescent mice exhibit greater locomotor sensitization to cocaine, and greater baseline anxiety responses that are alleviated by cocaine exposure compared to adult mice. 相似文献