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VN2222 (1-(benzo[b]thiophen-3-yl)-3-[4-(2-methoxiphenyl piperazin-1-yl]propan-1-ol) is a potential antidepressant with high affinity for the serotonin transporter and 5-HT(1A) receptors. Locally applied, VN2222 enhanced the extracellular 5-hydroxytryptamine (5-HT) concentration (5-HT(ext)) in rat striatum to 780% of baseline whereas its systemic administration (1-10 mg/kg s.c.) reduced 5-HT(ext). In the presence of citalopram, 8-OH-DPAT or VN2222 applied in medial prefrontal cortex reduced 5-HT(ext). Fluoxetine, VN2222, and 8-OH-DPAT suppressed the firing rate of dorsal raphe 5-HT neurons (ED(50): 790, 14.9, and 0.8 microg/kg i.v., respectively). These effects were antagonized by WAY 100635. Administration of VN2222 for 2 weeks desensitized 5-HT(1A) receptors as assessed by microdialysis and single-unit recordings (ED(50) values for 8-OH-DPAT were 0.45 and 2.34 microg/kg i.v. for controls and rats treated with 6 mg/kg day VN2222). These results show that VN2222 is a mixed 5-HT reuptake inhibitor/5-HT(1A) agonist that markedly desensitizes 5-HT(1A) autoreceptors. These properties suggest that it may be a clinically effective dual action antidepressant drug.  相似文献   
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End‐stage renal disease is a cause for death worldwide. Renal transplant is a therapeutic alternative, restricted by the scant number of donors. Function of the donor kidney is under risk of adverse circumstances such as fibrosis, where profibrotic effect of transforming growth factor beta 1 (TGF‐β1) plays a key role. Efforts to diminish risks of damage in the remnant kidney of the donor are required. Vitamin A represents one alternative. It has beneficial effects on some nephropathies, mainly those related to oxidative stress. It also participates in normal intrauterine renal development. We studied the effect of all‐trans retinoic acid (ATRA), active form of vitamin A, on postnephrectomy compensatory growth, in male or female rats. Compensatory growth and renal function were evaluated on four experimental groups: Control without treatment (CTL), ATRA‐treated intact rats (CTL + RA), nephrectomized rats (NFX), and ATRA‐treated nephrectomized rats (NFX + RA). We evaluated glomerular function (inulin clearance), tubular function (fractional excretions of sodium and potassium), and urinary flow. Renal mass was also estimated. In ATRA‐treated animals, compensatory growth was higher than in nephrectomized rats without treatment. Hyperfiltration after nephrectomy was less intense in ATRA‐treated female than in male rats. In tubular functions, effect of ATRA was more evident in female than in male rats. Glomerular expression of TGF‐β1 was lower in ATRA‐treated animals than in controls. ATRA reduced intensity and duration of compensatory changes after nephrectomy, improving recovery.  相似文献   
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ObjectiveWe developed a mobile cognitive test of verbal learning and memory, the mobile verbal learning test (mVLT), to allow for brief, repeated and portable delivery of a 12‐item list learning test through a smartphone. This study examined the psychometric properties of the mVLT among older persons with and without human immunodeficiency virus (HIV).MethodsSixty‐eight persons with HIV and 36 HIV‐negative individuals (aged 50–74) completed three trials of the mVLT on a smartphone once daily for 14 days. A different word list was administered each day.ResultsParticipants completed 80% of the 14 mVLT administrations, equating to 1166 valid and complete mVLTs. Neither adherence nor mean mVLT total score (number correct in 3 recall trials) differed by HIV status. No practice effects from repeated mVLT administration were observed, and there were moderately strong correlations of mVLT performance with performance on the in‐lab version of the task and with traditional cognitive assessments of cognitive processes contributing to memory. We found evidence of within‐person learning across mVLT trials, with persons with HIV demonstrating less learning from trials 1 to 3 compared to HIV‐negative participants.ConclusionsThe mVLT is a valid method to assess learning in the real world in older adults with and without HIV.  相似文献   
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BACKGROUND: The Hegemonic Medical Model is discussed and is articulated with the postulates of the sociology of the professions. The information takes Aids as a specific topic, because it involves the aspects of recent scientific development, of clinical and epidemiological importance and due to the research which is being done for its treatment and the production of immunizations. METHOD: This is a case study of students enrolled in different years of study for medical degrees at the three main universities in México City. A closed-question questionnaire was handed out, checked and corrected, the variables of which were related to three types of knowledge, that is, basic, technical and general. RESULTS: The students were revealed to master this subject to only a minor extent the extensions of the knowledge of the disciplines of the profession however being applied to new cases without the suitable accuracy. A certain degree of dissociation was found to exist among the different types of knowledge which were researched, the professional know-how having been noted to clearly conform within specialized, segmented, curative logic of the Hegemonic Medical Model. CONCLUSIONS: The technical, problem-solving knowledge employed in clinical use prevails over the systematic, abstract knowledge of the general knowledge of medicine. A clear notion of the processes based on the dominant medical pattern is revealed in the single-causal relations of the disease. There is an extension of the basic knowledge a the resolving of clinical problems. The medical students are oriented toward taking in knowledge which will be useful to them in clinical practice.  相似文献   
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For the technological advances in diagnostic and therapeutic procedures, the use of intravenous contrast media in the hospital is more and more frequent. It can produce acute renal failure secondary to its nephrotoxicity known as contrast media nephropathy. This review describes the pathophysiologic mechanisms of contrast media injury, including cytotoxicity caused by hyperosmoloarity of contrast media, the hemodynamic factors and the role of the renin-angiotensin system, prostaglandins, oxygen free radicals, endothelin-1, adenosine, nitric oxide and others. The understanding of this information is of vital importance for the development of prophylactic strategies for contrast media nephropathy.  相似文献   
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