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Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population 总被引:1,自引:0,他引:1
Abubaker J Jehan Z Bavi P Sultana M Al-Harbi S Ibrahim M Al-Nuaim A Ahmed M Amin T Al-Fehaily M Al-Sanea O Al-Dayel F Uddin S Al-Kuraya KS 《The Journal of clinical endocrinology and metabolism》2008,93(2):611-618
CONTEXT: Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC. OBJECTIVE: The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC. DESIGN: We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes. RESULTS: PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs. CONCLUSION: A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways. 相似文献
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Qi X Bakht S Leggett M Maxwell C Melton R Osbourn A 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(21):8233-8238
The evolution of the ability to synthesize specialized metabolites is likely to have been key for survival and diversification of different plant species. Oats (Avena spp.) produce antimicrobial triterpenoids (avenacins) that protect against disease. The oat beta-amyrin synthase gene AsbAS1, which encodes the first committed enzyme in the avenacin biosynthetic pathway, is clearly distinct from other plant beta-amyrin synthases. Here we show that AsbAS1 has arisen by duplication and divergence of a cycloartenol synthase-like gene, and that its properties have been refined since the divergence of oats and wheat. Strikingly, we have also found that AsbAS1 is clustered with other genes required for distinct steps in avenacin biosynthesis in a region of the genome that is not conserved in other cereals. Because the components of this gene cluster are required for at least four clearly distinct enzymatic processes (2,3-oxidosqualene cyclization, beta-amyrin oxidation, glycosylation, and acylation), it is unlikely that the cluster has arisen as a consequence of duplication of a common ancestor. Although clusters of paralogous genes are common in plants (e.g., gene clusters for rRNA and specific disease resistance), reports of clusters of genes that do not share sequence relatedness and whose products contribute to a single selectable function are rare [Gierl, A. & Frey, M. (2001) Planta 213, 493-498]. Taken together, our evidence has important implications for the generation of metabolic diversity in plants. 相似文献
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el-Sharnooby JA Ahmed LM 《The Egyptian journal of immunology / Egyptian Association of Immunologists》2003,10(2):57-66
Both qualitative and quantitative changes in mitochondrial DNA (mtDNA) have been implicated in the pathogenesis of diabetes mellitus. In this study, we investigate whether peripheral blood mtDNA (pb-mtDNA) is decreased and if there is any relation between its content and the parameters of both insulin resistance and secretion in offspring of diabetic subjects. The pb-mtDNA content was measured by real time polymerase chain reaction with mitochondrial- specific fluorescent probe, normalized by a nuclear DNA, 28S rRNA gene, in 42 offspring of type 2 diabetic patients and 12 age-, sex- and body mass index (BMI)-matched normal subjects. The correlations between pb-mtDNA content and the parameters of insulin resistance and secretion were studied. Our results indicated that the level of pb-mtDNA was lower in offspring of diabetic subjects than in control subjects (1230 +/- 0.05 vs. 1513 +/- 0.02 in the offspring and control subjects, respectively, P < 0.05). Also, pb-mtDNA content was significantly correlated with logarithmically transformed insulin sensitivity index (r = 0.5, P < 0.05), fasting C-peptide (r = -0.8, P < 0.05), acute insulin response (r = -0.8, P < 0.05) and late insulin response (r = -0.7, P < 0.05) in offspring of diabetic subjects. In conclusion, quantitative mtDNA status might be a hereditary factor associated with type 2 diabetes and is correlated negatively with indexes of insulin resistance and insulin secretion in offspring of diabetic patients. So, pb-mtDNA content could serve as an indicator of insulin sensitivity and insulin secretion in those subjects. 相似文献
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Edouard Cornet Cécile Tomowiak Aline Tanguy‐Schmidt Stéphane Lepretre Jehan Dupuis Pierre Feugier Alain Devidas Clara Mariette Véronique Leblond Catherine Thiéblemont Patricia Validire‐Charpy Laurent Sutton Emmanuel Gyan Jean‐Claude Eisenmann Pascale Cony‐Makhoul Loïc Ysebaert Xavier Troussard the Société Française d'Hématologie 《British journal of haematology》2014,166(3):390-400
A large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long‐term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio (SIR) of 1·86 (95% confidence interval (CI): 1·34–2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90–8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable. 相似文献
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