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111.
Although antidepressants have been used clinically for more than 50 years, no consensus has been reached concerning their precise molecular mechanism of action. Pharmacogenomics is a powerful tool that can be used to identify genes affected by antidepressants or by other effective therapeutic manipulations. Using this tool, others and we have identified as candidate molecular targets several genes or expressed sequence tags (ESTs) that are induced by chronic antidepressant treatment. In this article, we review antidepressant-elicited changes in gene expression, focusing especially on the remodeling of neuronal circuits that results. This refocusing motivates our hypothesis that this plasticity represents the mechanism for drug efficacy, and thus a causal event for clinical improvement. Defining the roles of these molecules in drug-induced neural plasticity is likely to transform the course of research on the biological basis of antidepressants. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression. Consideration of novel biological approaches beyond the "monoamine hypothesis" of depression is expected to evoke paradigm shifts in the future of antidepressant research.  相似文献   
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Closed ruptures of the flexor tendon have been described in association with distinct underlying pathologies. The spontaneous rupture of the flexor tendon secondary to axial tendon loading alone is infrequent. The previously reported cases with spontaneous rupture were mostly men aged 30 to 60 years. In addition, rupture occurred during manual labor with the fingers engaged in forceful or resisted flexion. Labor-associated forceful usage, in addition to gender and age, has been implicated in the pathogenesis of the stressful rupture of the flexor tendon. Here we report a case with spontaneous rupture of the flexor digitorum profundus (FDP) and superficialis of the index finger as well as the flexor pollicis longus (FPL). Unlike the previously reported cases the present patient was an elderly woman engaged in no apparent occupational activities. In the present case, however, the patient had a particular predisposing condition. The patient used only the right hand during her whole lifetime because of a perinatal brachial plexus injury on the contralateral arm. The present case may show that the tendons of an elderly patient could yield to the axial loading of normal levels of activities of daily living when the usage is as incessant as in the present patient.  相似文献   
114.
INTRODUCTION: We previously developed a noninvasive video urodynamic study using color Doppler ultrasonography. We sought the best flow velocity-related parameter which would allow prediction of an improvement in lower urinary tract symptoms (LUTS) after alpha 1-blocker treatment. METHODS: Twenty-two men with benign prostatic hyperplasia who were treated with a nonselective alpha 1-blocker (urapidil) were included. Subjective symptoms were evaluated using the International Prostate Symptom Score (IPSS) before and after alpha 1-blocker treatment. We measured the flow velocities using a transperineal ultrasound technique in the distal prostatic urethra just proximal to the external urethral sphincter (V1) and in the sphincteric urethra (V2), and used them to obtain the velocity ratio (VR=V1/V2). The corresponding functional cross-sectional areas of the urethra at these two sites (A1 and A2) were calculated as Q(max)/V. All these parameters obtained by the velocity-flow urodynamics were compared before treatment and after 4 weeks. RESULTS: After treatment, V1 and VR were decreased, and A1 was increased. V2 correlated best with the change in IPSS before and after alpha 1-blocker therapy, with Spearman's rho of 0.584. All men with V2 exceeding 50 cm/s did not show an improvement in the LUTS. CONCLUSIONS: The maximum flow velocity at the sphincteric urethra (V2) can predict the subjective outcome of alpha 1-blocker treatment. The velocity-flow parameters changed after alpha 1-blocker treatment. We confirmed that the transperineal ultrasound urodynamic study is not only noninvasive but also informative.  相似文献   
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BACKGROUND: Previous randomized trials have shown a survival advantage of concurrent platinum-based chemoradiotherapy with or without adjuvant chemotherapy for advanced nasopharyngeal cancer. Applicability of these data to a Japanese population is an important issue which remains to be solved. METHODS: A retrospective survey of treatment of patients with nasopharyngeal cancer in 17 institutions in Japan was done with special reference to the relationship between the type of chemotherapy and survival outcome. Chemotherapy used was classified according to: (i) whether > or =2 courses of platinum plus 5-fluorouracil (FP) was given; or (ii) whether platinum was administered concurrently with radiotherapy (RT). This resulted in three groups being produced consisting of (i)/(ii) = YES/YES, other miscellaneous (MISC) and RT alone. RESULTS: Of 333 evaluable replies, 67 patients (20%) corresponded to the YES/YES, 192 (58%) to the MISC and 74 (22%) to the RT alone group. The YES/YES group achieved a better overall survival than RT alone for patients with intermediate stage (T3N0 or T1-3N1, 81.9 versus 60.7% at 5 years, P = 0.042) and advanced stage (T4 or N2/3, 56.6 versus 31.5%, P = 0.017) disease. The MISC group achieved an almost identical survival rate to that in the YES/YES group for patients with intermediate stage disease (81.9% at 5 years, P = 0.968), whereas it was not significantly different from that of the RT alone group for patients with advanced stage disease (44.0%, P = 0.261). CONCLUSION: The results of this survey mirrored the data from previous randomized trials for patients with intermediate and advanced stage nasopharyngeal cancer in Japan. However, confirmatory prospective trials are required to test the efficacy of less toxic approaches for patients with intermediate stage disease.  相似文献   
117.
Combined therapy with a fixed-tumor cell vaccine and intratumoral injection of NK cells induced strong tumor regression of rat glioma. Rat 9L glioma cells were inoculated into syngeneic male rats at the flank (subcutaneous tumor model) or at the basal ganglia of the right hemisphere (intracranial tumor model). Rats were intradermally injected three times with vaccine comprising fixed 9L cells, IL-2- and GMCSF-microparticles, and tuberculin prior to (protective studies) or after (therapeutic studies) challenge with live 9L cells. In the protective studies, the vaccine alone achieved significant tumor growth inhibition and elongation of mean life span in both the subcutaneous and intracranial tumor models. No therapeutic effect was observed in the intracranial tumor model with the vaccine alone. However, intratumoral injection of rat NK cells strongly assisted the therapeutic effect of the vaccine in the brain tumor model and resulted in a statistically significant elongation of life span. We propose that intratumoral injection of NK cells may not only kill brain tumor cells directly, but also trigger a strong immune response in the focal lesion of the brain after vaccination. (Cancer Sci 2004; 95: 98–103)  相似文献   
118.
The relationship between the cord blood level of IgE specific for Dermatophagoides pteronyssinus (Dp-IgE) and the development of allergic disorders in infants was investigated. None of the 10 infants who had no family history of allergic disorders and a cord blood Dp-IgE level of <0.07 IU/ml developed atopic dermatitis by 10 months of age. Among the infants whose mothers had atopy, those with a cord blood Dp-IgE level of > or =0.07 IU/ml showed a higher prevalence of allergic disorders at 3 years of age than those with a cord blood Dp-IgE level of <0.07 IU/ml. These observations suggest that the cord blood Dp-IgE level may be related to allergic manifestations in infancy.  相似文献   
119.
A 9-year-old girl presented with a subarachnoid hemorrhage. Cerebral angiography showed a saccular aneurysm arising from the horizontal portion of the right middle cerebral artery. The aneurysm was successfully clipped, and the dome of the aneurysm was excised for pathological study. Histological examination of the aneurysm wall showed that the entire thickness of the wall showed an increased myxoid degeneration. No dissection was present. Most intracranial aneurysms in childhood are believed to be of the saccular type similar to that in adults, but the pathogenesis of the aneurysm formation remains controversial. Myxoid degeneration may cause intracranial saccular aneurysm with eventual rupture, even in the absence of dissection. This is the first case reported of a ruptured saccular aneurysm caused by myxoid degeneration in a child. The possible pathophysiology is discussed.  相似文献   
120.
We report a case of a holocord high-intensity lesion extending from L1 up to the medulla oblongata on T2-weighted spinal magnetic resonance imaging (MRI) associated with an intramedullary spinal abscess secondary to an infected dermoid cyst. The intraoperative findings revealed that the high-intensity lesion on the T2-weighted image was edematous tissue. The MRI change in the spinal cord gradually improved in response to the use of postoperative antibiotics. The change was considered to represent reversible inflammatory changes, as there was no neurological deficit found at the cervical level and it resolved after surgery and medical treatment. The pathomechanism is discussed herein.  相似文献   
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