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Aims/hypothesis Type 2 diabetes is characterised by excessive hepatic glucose production and frequently leads to systemic vascular complications. We therefore analysed the relationship between the gene expression profile in the liver and the pathophysiology of Type 2 diabetes.Methods Liver biopsy samples were obtained from twelve patients with Type 2 diabetes and from nine non-diabetic patients. To assay gene expression globally in the livers of both groups, we made complementary DNA (cDNA) microarrays consisting of 1080 human cDNAs. Relative expression ratios of individual genes were obtained by comparing cyanine 5-labelled cDNA from the patients with cyanine 3-labelled cDNA from reference RNA from the liver of a non-diabetic patient.Results On assessing the similarities of differentially expressed genes, the gene expression profiles of the twelve diabetic patients formed a separate cluster from those of the non-diabetic patients. Of the 1080 genes assayed, 105 (9.7%) were up-regulated and 134 (12%) were down-regulated in the diabetic livers (p<0.005). The genes up-regulated in the diabetic patients included those encoding angiogenic factors such as vascular endothelial growth factor, endothelin and platelet-derived growth factor. They also included TGF superfamily genes such as TGFA and TGFB1 as well as bone morphogenetic proteins. Among the down-regulated genes in the diabetic patients were molecules defending against stress, e.g. flavin-containing monooxygenase and superoxide dismutase.Conclusions/interpretation These findings suggest that livers of patients with Type 2 diabetes have gene expression profiles indicative of an increased risk of systemic vascular complications.Electronic Supplementary Material Supplementary material is available in the online version of this article at Abbreviations aRNA
antisense RNA
- BMP
bone morphogenetic protein
- cDNA
complementary DNA
- Cy
cyanine
- FMO
flavin-containing monooxygenase
- NASH
non-alcoholic steatohepatitis
- PDGF
platelet-derived growth factor
- SSC
standard saline citrate
- SOD
superoxide dismutase
- VCAM
vascular cell adhesion molecule
- VEGF
vascular endothelial growth factor 相似文献
85.
Takuma Kohsaka Takaaki Hiragun Kaori Ishii Makiko Hiragun Akiko Kamegashira Michihiro Hide 《Allergology international》2018,67(1):103-108
Background
Atopic dermatitis (AD) is exacerbated by sweating, and the skin of most patients with AD are resided by Malassezia (M.) fungi. Recently, MGL_1304 produced by Malassezia globosa was identified as the major histamine releasing antigen in human sweat.Methods
The full length cDNA of the counterpart of MGL_1304 in Malassezia restricta (Mala r 8), was cloned by degenerate PCR and rapid identification of cDNA ends (RACE). Recombinant MGL_1304, and its counterparts, Mala s 8 (produced by Malassezia sympodialis) and Mala r 8 were prepared, and compared in their allergenicities by dot blot analysis and histamine release tests with sera and basophils of patients with AD.Results
The identities between MGL_1304 and Mala s 8, MGL_1304 and Mala r 8, and Mala s 8 and Mala r 8 were 68%, 78%, and 76%, respectively, in protein sequences. Dot blot analysis revealed that the level of IgE binding to Mala s 8 was higher than that of MGL_1304. However, histamine release tests revealed that MGL_1304 and Mala r 8 possessed higher activity than Mala s 8. In addition, the crude lysate of M. globosa showed higher histamine release ability than that of M. sympodialis.Conclusions
Patients with AD showed hypersensitivities against MGL_1304 and its homologs. However, the allergenicities of the homologs are variable and the histamine release activities may be different from the solid-phase binding activities for IgE. Sweat allergy should be carefully evaluated with biological activities of MGL_1304 and its homologs of other Malassezia fungi residing on the skin. 相似文献86.
丙型肝炎5''''非编码区末端快速基因扩增方法的建立及应用 总被引:1,自引:0,他引:1
目的 建立快速获得丙型肝炎(HCV)基因组5’非编码区(5’uTR)真末端序列的分子生物学方法。方法 逆转录后利用末端聚合酶(TOT)进行加尾反应,再利用套式聚合酶链反应(PCR)扩增出目的末端基因的cDNA片段,A-T克隆,用限制性内切酶片段长度多态性分析(RVLP)与PCR鉴定重组子,全自动序列分析仪测定插入子序列。结果 cDNA末端快速扩增技术(RACE)获得5株HCV5’UTR克隆,包括3株全长克隆和2株缺失克隆。2株缺失克隆,一条在5’末端缺失53个碱基,另一条缺失144个碱基。结论 RACE技术快速、有效、实用,可有效获得丙型肝炎病毒基因组的5’非编码区末端序列。 相似文献
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Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction 总被引:1,自引:0,他引:1
《Vaccine》2015,33(33):4069-4080
Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980s. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV-MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990s, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork producers and biologics companies. 相似文献
89.
Towards a molecular approach to gastric cancer management 总被引:1,自引:0,他引:1
Abstract
Gastric cancer is a leading cause of cancer death worldwide. Most patients with gastric cancer present with locally advanced and incurable disease, and overall survival is poor. Considerable research efforts towards the epidemiology and pathogenesis of gastric cancer have not been translated into treatment success. We discuss current concepts of the pathogenesis of gastric cancer and how recent research advances, in particular global gene expression strategies, may improve this understanding, and suggest a framework wherein these approaches may be used. (Intern Med J 2001; 31: 296–303) 相似文献
Gastric cancer is a leading cause of cancer death worldwide. Most patients with gastric cancer present with locally advanced and incurable disease, and overall survival is poor. Considerable research efforts towards the epidemiology and pathogenesis of gastric cancer have not been translated into treatment success. We discuss current concepts of the pathogenesis of gastric cancer and how recent research advances, in particular global gene expression strategies, may improve this understanding, and suggest a framework wherein these approaches may be used. (Intern Med J 2001; 31: 296–303) 相似文献
90.
Localization and immunogenicity of tubulin in the filarial nematodes Brugia malayi and B. pahangi 总被引:1,自引:0,他引:1
R. HELM M. E. SELKIRK J. E. BRADLEY R. G. BURNS† A. J. HAMILTON‡ S. CROFT§ R. M. MAIZELS 《Parasite immunology》1989,11(5):479-502
Tubulin was identified in the filarial nematodes Brugia malayi and B. pahangi by several approaches. Initially, a monoclonal antibody (6D8) was selected for its unusual binding to B. malayi microfilariae in indirect immunofluorescence assays: 6D8 showed granular, heterogeneously dispersed fluorescence on fixed parasites but did not bind to unfixed microfilariae. The microfilarial sheath did not bind 6D8, although it did bind fluoresceinated wheatgerm agglutinin. By Western blotting against microfilarial sonicate, 6D8 reacted with a 50,000-55,000 mol. wt protein, and also bound to purified chicken brain beta-tubulin. Additionally, this monoclonal antibody reacted with a recombinant fusion protein expressed by a clone (Bpa-7) originally isolated from an adult B. pahangi cDNA expression library by its reaction with chronic human filariasis serum. This clone encodes a small 40 amino acid C-terminal segment corresponding to residues 409-449 of beta-tubulin, and shows complete amino acid sequence homology with vertebrate beta-tubulin from 409 to 430 but 55% divergence (six amino acid substitutions, four insertions and one deletion) from human and chicken beta-tubulin over positions 431-449 at the C terminus. Antibody to both parasite and vertebrate (chicken) tubulin was found in filarial infection sera, with higher levels of autoreactive antibody apparent in amicrofilaraemic individuals. Immunogold electron microscopy was then used to localize beta-tubulin in B. malayi microfilariae and adult worms. Tubulin was shown not to be exposed on the microfilarial sheath or in the cuticle of either stage, but was found to be abundant in the somatic tissues. In microfilariae, 6D8 bound myofibril structures under the hypodermal layer, and also bound within cell nuclei. In the adult stage, tubulin was associated with muscle blocks, as well as the intestinal brush border and the embryonic uterine microfilariae. 相似文献