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91.
目的探讨自发性高血压大鼠颈动脉中抑癌基因P53和原癌基因c-jun、c-fos、c-myc mRNA的表达.方法用逆转录聚合酶链式反应检测两种基因的表达水平.正常雄性大鼠作为对照组.结果 SHR颈动脉中,抑癌基因P53和原癌基因c-jun、c-fos、c-myc均有高表达,较WKY差异有显著性(P<0.05).结论自发性高血压大鼠颈动脉组织中抑癌基因P53和原癌基因c-jun、c-fos、c-myc均有高表达,癌基因的活化可能与自发性高血压大鼠颈动脉血管重构有关. 相似文献
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The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase
activity is responsible for both therapeutic and side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacological
results with developmental compounds suggest that COX-2 is the relevant target for the therapeutic (i.e. anti-inflammatory)
effects of NSAIDs, whereas gastric and renal side-effects are related to inhibition of constitutive COX-1. However a role
of COX-1 in inflammation cannot be excluded. Furthermore, more research effort is needed to investigate the functional relevance
of COX-2 in normal tissue. 相似文献
95.
Sinusoids are found not only in the normal liver but also in certain liver tumours, including hepatoblastoma, the most common malignant liver tumour in childhood. In this study, sinusoids in 12 hepatoblastomas, of various subtypes, and in normal liver were investigated with UEA-1 and antibodies against von Willebrand's factor, CD31 and CD34 to detect differences of possible diagnostic significance. In the normal liver, staining of sinusoids was seen with all these markers, but it was focal and confined to a few sinusoids near the portal tracts. In hepatoblastoma, the endothelial markers reacted with the sinusoids to varying extents. UEA-1 and anti-CD34 usually stained the majority of these vessels, anti-CD34 staining greater numbers of sinusoids and with greater intensity. Immunostaining revealed that both number and spatial organization of sinusoids in hepatoblastoma are dependent on the subtype. In addition to staining of endothelium, one of the two small cell hepatoblastomas exhibited strong immunoreactivity of the tumour cells for CD34. These findings show that the marked difference in sinusoidal immunoreactivity for CD34 between normal liver and hepatoblastoma could be useful for discriminating between non-neoplastic liver tissue and highly differentiated fetal hepatoblastoma. Our findings also show that small cell hepatoblastoma, in addition to acute leukaemia, should be considered when immunoreactivity for CD34 is found in small round and blue cell tumours in childhood. 相似文献
96.
Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesotheliomas. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulopapillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thromobomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours. 相似文献
97.
G. Wu S. F. Fan Z.-H. Lu R. W. Ledeen S. M. Crain 《Journal of neuroscience research》1995,42(4):493-503
Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via Gs regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K+ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the Gs/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc. 相似文献
98.
Dr. S. Eggstein MD G. Manthey MT T. Hirsch PhD F. Baas MA B. U. V. Specht MD E. H. Farthmann MD 《Digestive diseases and sciences》1996,41(6):1069-1075
Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr). 相似文献
99.
M. Vrethem B. Lindvall S. Kihlstrand E. Bckman T. Brismar P. Fredman K.G. Henriksson 《European journal of neurology》1996,3(2):156-159
We report improvement in muscle strength in a patient with multifocal motor neuropathy (MMN) when given high-dose intravenous immunoglobin (i.v.-Ig) treatment. The patient had asymmetrical limb weakness, atrophy and absent or weak reflexes, but no sensory disturbances. Neurography showed multiple conduction blocks in peripheral motor nerves but no sensory nerve abnormalities. Serum and anti-GM1 antibodies were not found, however, the patient had serum antibodies against the glycolipid LK1, an epitope found both in glycolipid and also in some glycoproteins in peripheral nerve myelin. Muscle strength improved 5 days after i.v.-Ig therapy, and lasted about 10 weeks. Repeated courses of treatment resulted in similar improvement. This is, to our knowledge, the first patient reported with MMN found to have antibodies against the glycolipid LK1. 相似文献
100.
Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals. 相似文献