全文获取类型
收费全文 | 8566篇 |
免费 | 930篇 |
国内免费 | 321篇 |
专业分类
耳鼻咽喉 | 38篇 |
儿科学 | 165篇 |
妇产科学 | 57篇 |
基础医学 | 1218篇 |
口腔科学 | 577篇 |
临床医学 | 756篇 |
内科学 | 1449篇 |
皮肤病学 | 166篇 |
神经病学 | 391篇 |
特种医学 | 146篇 |
外国民族医学 | 2篇 |
外科学 | 534篇 |
综合类 | 1610篇 |
现状与发展 | 5篇 |
预防医学 | 448篇 |
眼科学 | 255篇 |
药学 | 369篇 |
14篇 | |
中国医学 | 1345篇 |
肿瘤学 | 272篇 |
出版年
2024年 | 49篇 |
2023年 | 161篇 |
2022年 | 340篇 |
2021年 | 437篇 |
2020年 | 445篇 |
2019年 | 333篇 |
2018年 | 253篇 |
2017年 | 339篇 |
2016年 | 336篇 |
2015年 | 334篇 |
2014年 | 606篇 |
2013年 | 656篇 |
2012年 | 529篇 |
2011年 | 595篇 |
2010年 | 532篇 |
2009年 | 410篇 |
2008年 | 424篇 |
2007年 | 394篇 |
2006年 | 410篇 |
2005年 | 348篇 |
2004年 | 288篇 |
2003年 | 234篇 |
2002年 | 221篇 |
2001年 | 173篇 |
2000年 | 125篇 |
1999年 | 85篇 |
1998年 | 103篇 |
1997年 | 77篇 |
1996年 | 85篇 |
1995年 | 58篇 |
1994年 | 55篇 |
1993年 | 52篇 |
1992年 | 48篇 |
1991年 | 45篇 |
1990年 | 31篇 |
1989年 | 32篇 |
1988年 | 14篇 |
1987年 | 25篇 |
1986年 | 19篇 |
1985年 | 27篇 |
1984年 | 9篇 |
1983年 | 13篇 |
1982年 | 16篇 |
1981年 | 12篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 9篇 |
1975年 | 3篇 |
排序方式: 共有9817条查询结果,搜索用时 78 毫秒
51.
Miki Kaneko Toshikazu Uchida Mitsuhiko Moriyama Yasuyuki Arakawa Toshio Shikata Kenichiro Gotoh Satoaki Mima 《Journal of medical virology》1995,47(3):204-208
A pathogenic role of precore-defective mutation in the onset of fulminant hepatitis B has been suggested. However, precore-defective mutants do not always cause fulminant hepatitis B and are not always isolated from affected patients. These findings strongly suggest the presence of some additional important mutations outside the precore region in fulminant hepatitis. In the present investigation an attempt was made to sequence the X open reading frame of hepatitis B virus DNA isolated from seven patients with fulminant hepatitis B and five patients with acute hepatitis B. The latter were used as controls. Since the X open reading frame encodes the X protein and contains the core promoter/enhancer II complex, some critical mutations may enhance or disrupt the replication and expression of hepatitis B virus DNA leading to fulminant hepatitis. A C-to-T substitution was found at nucleotide (nt) 1655, an A-to-T substitution at nt 1764 and a G-to-A substitution at nt 1766 in 4, 5 and 5 patients, respectively, out of the seven with fulminant hepatitis. These substitutions were not recognized in the patients with acute hepatitis. These mutations might change the function of the X protein and core promoter/enhancer II complex. It is suggested, therefore, that these mutations, as well as the precore-defective mutation, may play an important role in the pathogenesis of fulminant hepatitis. © Wiley-Liss, Inc. 相似文献
52.
S. Sakurada O. Shido N. Sugimoto K. Fujikake T. Nagasaka 《Pflügers Archiv : European journal of physiology》1994,429(2):291-293
Rats were subjected to an ambient temperature (Ta) of 33°C for ca. 5 h during the last half of the dark phase for 5, 14 or 28 consecutive days (heat-exposed rats, HE), while control rats were kept at a constant Ta of 24°C. After the heat exposure schedule, the levels of hypothalamic temperature (Thy) as an index of body core temperature in the HE were significantly lower than those of the controls for 2–4 h in the last half of the dark phase. The low levels of Thy persisted during the specific period for 1, 3 and 6 days after the end of the 5-, 14- and 28-day heat exposure schedules, respectively. These results confirm that, in rats subjected to daily heat exposure for ca. 5 h at a fixed time per day, their Thy falls during the period when the rats were previously exposed to heat, and suggest that the duration of the specific Thy change observed after completing the heat exposure schedule depends on the length of the heat exposure schedule. 相似文献
53.
Rabies virus binding at neuromuscular junctions 总被引:4,自引:0,他引:4
Morphological, immunocytochemical, biochemical, and immunological techniques have been used to describe rabies virus binding to a sub-cellular unit and molecular complex at the neuromuscular junction (NMJ). Early after infection in vivo, virus antigen and virus particles were found by immunofluorescence, electron microscopy and immunoelectron microscopy in regions of high density acetylcholine receptors (AChR) at NMJs. One monoclonal antibody (alpha-Mab) to the alpha subunit of the AChR blocked attachment of radio-labeled rabies virus to cultured muscle cells bearing high density patches of AChR. A sub-cellular structure, resembling an array of AChR monomers, bound both rabies virus antigens and alpha-Mab. By immunoblotting with electrophoretically transferred motor endplate proteins, rabies virus proteins and alpha-Mab bound to two proteins of 43 000 and 110 000 daltons. A rabies virus glycoprotein antibody detected virus antigen bound to the 110 000 dalton protein. An auto-immune (anti-idiotypic) response followed immunization of mice with rabies virus glycoprotein antigen; the antibody was directed to the 110 000 dalton protein. This auto-antibody altered the kinetics of neutralization by rabies virus antibody and induced the formation of rabies virus antibody after inoculation of mice. These results define, at the neuromuscular junction, a rabies virus receptor which may be part of the acetylcholine receptor complex. 相似文献
54.
Cytomegalovirus infection after orthotopic liver transplantation is restricted by a pre-existing antiviral immune response of the recipient 总被引:1,自引:0,他引:1
Infection of the liver by the human cytomegalovirus (HCMV) frequently occurs after orthotopic liver transplantation (OLT). However, the role of viral replication and the inflammatory reaction in the development of HCMV-associated liver dysfunction is unclear. To address this question in vivo, 84 liver biopsy specimens from 74 patients who received an orthotopic liver transplant were investigated by immunohistochemical detection of viral antigens and cell type specific marker proteins. The extent of viral replication was correlated with the HCMV antibody status of donor and recipient. HCMV immediate early antigens were found in 25 of 84 liver tissue sections investigated, hepatocytes being the predominant target cells. Bile duct epithelial cells, endothelial cells, mesenchymal cells and sinusoidal lining cells were also found susceptible to HCMV infection. The detection of viral capsid antigens, nuclear inclusions in infected cells and foci of infected cells were suggestive of permissive infection in these cells. In 25 HCMV-positive liver biopsy specimens, the median extent of HCMV infection was 0.33 (0.02-5.67) infected cells/mm(2) liver tissue. Primary infection of liver transplant recipients (D+/R-) was associated with a significantly higher extent of organ involvement as compared to reinfection or reactivation (D+/R+). In contrast, the extent of inflammatory infiltrates in areas of infected liver cells was higher in tissues of patients with pre-existing immunoreactivity (R+) compared to patients without pre-existing immunoreactivity (R-). In conclusion, these results favour the assumption that the immune response to HCMV is effective in restricting viral spread in the liver. 相似文献
55.
丙型肝炎病毒核心蛋白在HepG2细胞中的表达及其对端粒酶活性的影响 总被引:2,自引:0,他引:2
目的 建立HCV核心蛋白细胞表达模型,并探讨其对细胞端粒酶活性的影响。方法 用PCR法扩增出HCV核心基因cDNA,将其插入真核表达载体pBK-CMV的HindⅢ和BamHⅠ位点间,构建重组质粒pBK-HCVc。再将重组质粒pBK-HCVc和空载体分别导入肝癌细胞株HepG2中,G418筛选,RT-PCR、免疫组化和蛋白印迹鉴定HCV核心蛋白表达。PCR-ELISA法检测端粒酶活性。结果 构建的pBK-HCVc质粒在HepG2细胞中有稳定表达。表达HCV核心蛋白的细胞HepG2-C的端粒酶活性较转染空载体的细胞HepG2-CMV明显升高。结论 HCV核心蛋白上调了端粒酶活性,可能是HCV诱发肝细胞癌的一种途径。 相似文献
56.
Molecular and serological evaluation of surface antigen negative hepatitis B virus infection in blood donors from Venezuela 总被引:2,自引:0,他引:2
Gutiérrez C Devesa M Loureiro CL León G Liprandi F Pujol FH 《Journal of medical virology》2004,73(2):200-207
Surface antigen negative hepatitis B virus (HBV) infection was evaluated in Venezuela, by molecular characterization of blood samples positive for antibodies to core antigen (anti-HBc) and negative for surface antigen (HBsAg) in blood donors (residual infections). HBV DNA was found in 11/258 samples (4.3%), and was significantly associated with high levels of anti-HBc antibodies (>25 UI/ml, P < 0.05), while no correlation was found between the presence of HBV DNA and the levels of anti-HBs. Synonymous and non-synonymous mutations were found in the HBV surface region (but not vaccine escape mutants) and in the precore/core region (precore mutants in 2/7 samples and 33-45 bp deletions near the N-terminal core region in 4/19 samples). While HBV genotype F prevails among HBsAg positive samples from blood donors in Venezuela, residual infection isolates were mainly genotypes A and D. Phylogenetic analysis of viral surface and core region revealed discrepancies in genotype designation in 6/9 samples, suggesting the presence of mixed infection or recombination. In conclusion, HBV residual infection in Venezuela does not seem to be frequently observed in HBV genotype F. This type of infection is frequently associated with variants exhibiting mutations in the surface gene that might be affecting the correct recognition by commercial tests, with precore mutants and with core internal deletions. These variants do not seem to cause severe liver disease, and on the contrary, were found circulating at low viremia. 相似文献
57.
Transcription from the gene encoding the herpesvirus entry receptor nectin-1 (HveC) in nervous tissue of adult mouse 总被引:13,自引:0,他引:13
Hepatitis C virus core protein, in addition to being a component of the viral capsid, has a number of regulatory functions. Here we showed two bodies of evidence indicating that a fraction of the core protein species is a substrate of the ubiquitin (Ub)-proteasome pathway of targeted proteolysis. First, the core protein processing the C-terminal hydrophobic region is metabolically unstable, and incubation with a proteasome inhibitor led to a significant accumulation of the protein. Second, an in vivo ubiquitylation assay indicates conjugation of multi-Ub chain to the unstable core protein. In contrast, a stable form of core protein, p21, is also able to be ubiquitylated, but it links to a single or only a few Ub moiety. Therefore, processing event(s) at the C-terminal hydrophobic domain of HCV core protein may affect the ubiquitylation pathway, particularly the efficiency of the multi-Ub chain assembly, resulting in stable, matured core proteins. 相似文献
58.
Lymphocyte proliferative responses to chlamydial antigens in human chlamydial eye infections. 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Clinical and experimental immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
D C Mabey M J Holland N D Viswalingam B T Goh S Estreich A Macfarlane H M Dockrell J D Treharne 《Clinical and experimental immunology》1991,86(1):37-42
In order to study the relationship between cell-mediated immune responses to Chlamydia trachomatis and the pathogenesis of human chlamydial eye disease, we have measured the peripheral blood lymphocyte proliferative responses to whole chlamydial elementary bodies in 40 subjects with oculogenital chlamydial infection of varying severity, 13 subjects with genital chlamydial infections and 12 healthy seronegative controls. The mean stimulation index was significantly higher in those with oculogenital infections than in controls. There was a strong correlation between the response to C. trachomatis serotypes B and L1. We studied the relationship between proliferative responses and four clinical parameters: follicular conjunctivitis, papillary hypertrophy, corneal pannus and epithelial punctate keratitis, but were unable to show a significant association with any of these. Nor was there any association between proliferative response and serum antibody titre to C. trachomatis (pooled serotypes D-K), duration of disease or quantitative isolation of chlamydia from the conjunctiva. The depletion of CD8+ cells had no consistent effect on proliferative responses to serotype L1 in 13 subjects. 相似文献
59.
Robert D. Nicholls 《American journal of medical genetics. Part A》1993,46(1):16-25
Although Angelman (AS) and Prader-Willi (PWS) syndromes are human genetic disorders with distinctly different developmental and neurobehavioural phenotypes, they both have abnormalities in inheritance of chromosome 15q11–q13. Whether AS or PWS arises depends on the parental origin of a deletion or uniparental disomy (the inheritance of 2 copies of a genetic locus from only one parent) for 15q11–q13. Normal development requires a genetic contribution for this genetic region from both a male and female parent. The dependence on parental origin implies that genes in human 15q11–q13 have distinct functions depending upon epigenetic, parent-of-origin differences, known as genomic imprinting. Here, I review the role of uniparental disomy and genomic imprinting in the pathogenesis of AS and PWS, and briefly discuss phenotype-genotype correlations using candidate genes and mouse models, in particular for hypopigmentation. © 1993 Wiley-Liss, Inc. 相似文献
60.
Cardiac ankyrin repeat protein (CARP), which is structurally characterized by the presence of four ankyrin repeat motifs in its central region, is believed to be localized in the nucleus and to participate in the regulation of cardiac-specific gene expression in cardiomyocytes. However, we recently found that CARP was induced in skeletal muscle by denervation, leading us to speculate that CARP may be induced under some pathological conditions. In the present study, we immunohistochemically analyzed the expression of CARP in 11 cases of spinal muscular atrophy (SMA) and 14 cases of congenital myopathy. In SMA, CARP was expressed selectively in severely atrophic myofibers, suggesting that CARP expression may reflect the status of muscle atrophy. Furthermore, in the congenital myopathies, the expression patterns of CARP were distinct among the subtypes, which included nemaline myopathy, myotubular myopathy, central core disease, and congenital fiber type disproportion. Although CARP was preferentially expressed in severely damaged myofibers in nemaline myopathy, it was not detected in central core disease. These findings suggest that immunohistochemical evaluation of CARP may be helpful in the diagnosis of SMA and the congenital myopathies. 相似文献