全文获取类型
收费全文 | 642篇 |
免费 | 93篇 |
国内免费 | 13篇 |
专业分类
儿科学 | 7篇 |
妇产科学 | 3篇 |
基础医学 | 120篇 |
口腔科学 | 4篇 |
临床医学 | 74篇 |
内科学 | 241篇 |
皮肤病学 | 1篇 |
神经病学 | 18篇 |
特种医学 | 7篇 |
外科学 | 34篇 |
综合类 | 37篇 |
现状与发展 | 2篇 |
预防医学 | 114篇 |
眼科学 | 3篇 |
药学 | 43篇 |
中国医学 | 5篇 |
肿瘤学 | 35篇 |
出版年
2023年 | 17篇 |
2022年 | 12篇 |
2021年 | 37篇 |
2020年 | 124篇 |
2019年 | 56篇 |
2018年 | 63篇 |
2017年 | 86篇 |
2016年 | 70篇 |
2015年 | 93篇 |
2014年 | 65篇 |
2013年 | 29篇 |
2012年 | 9篇 |
2011年 | 1篇 |
2010年 | 15篇 |
2009年 | 21篇 |
2008年 | 3篇 |
2007年 | 7篇 |
2006年 | 2篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1996年 | 6篇 |
排序方式: 共有748条查询结果,搜索用时 625 毫秒
2.
3.
ABSTRACTThe H7 subtype avian influenza virus (AIV) has been reported to infect not only poultry but also humans. The haemagglutinin (HA) protein is the major surface antigen of AIV and plays an important role in viral infection. In this study, five monoclonal antibodies (mAbs, 2F8, 3F6, 5C11, 5E2 and 5C12) against the HA protein of H7 virus were produced and characterized. Epitope mapping indicated that 103RESGSS107 was the minimal linear epitope recognized by the mAbs 2F8/3F6/5C11, and mAbs 5E2/5C12 recognized the epitope 103-145aa. The protein sequence alignment of HA indicated that the two epitopes were not found in other subtypes of AIV, and none of the five mAbs cross-reacted with other subtypes, suggesting these mAbs are specific to H7 virus. The epitope 103RESGSS107 was highly conserved among Eurasian lineage strains of H7 AIV, whereas three amino acid substitutions (E104R, E104K and E104G) in the epitope occurred in 98.44% of North-American lineage strains. Any of these single mutations prevented the mutated epitope from being recognized by mAbs 2F8/3F6/5C11; thus, these mAbs can distinguish between Eurasian and North-American lineages of H7 strains. Furthermore, the mAbs 2F8, 3F6 and 5C11 could be highly blocked with H7-positive serum in blocking assays, revealing that 103RESGSS107 may be a dominant epitope stimulating the production of antibodies during viral infection. These results may facilitate future investigations into the structure and function of HA protein, as well as surveillance and detection of H7 virus.RESEARCH HIGHLIGHTS
Five mAbs against HA protein of H7 AIV were generated and characterized.
Two novel epitopes 103RESGSS107 and 103-145aa were identified.
The epitope 103RESGSS107 differs between Eurasian and North-American lineages.
The mAbs 2F8, 3F6 and 5C11 could distinguish two lineages of H7 strains.
4.
Ruoheng Yang Qingwei Liu Wei Pang Fei Gao Huabin Liang Wei Zhang Yalong Lin Min Li Zhihua Liu George F. Gao Linqi Zhang Hui Xiao Yongtang Zheng Zhong Huang Xia Jin 《Vaccine》2021,39(6):915-925
Zika virus (ZIKV) infection has caused major public health problems recently. To develop subunit vaccines for ZIKV, we have previously constructed recombinant ZIKV envelope protein domain III (EDIII), and the entire ectodomain (E80, which comprises EDI, EDII and EDIII), as vaccine candidates and showed both of them being immunogenic and protective in murine models. In this follow-up study, we compared these vaccine candidates in non-human primates. Both of them elicited neutralizing antibody responses, but only E80 immunization inhibited ZIKV infection in both peripheral blood and monkey tissues, whereas EDIII increased blood ZIKV RNA through possibly antibody-dependent enhancement. Further investigations revealed that the virion-binding antibody response in E80 immunized monkeys persisted longer and stronger than in EDIII immunized monkeys. These results demonstrate that E80 is superior to EDIII as a vaccine candidate, and that the magnitude, quality and durability of virion-binding neutralizing antibodies are correlates of protection. 相似文献
5.
6.
《Immunobiology》2017,222(2):394-398
It has been established that mesenchymal stem cells (MSCs) can have a suppressive effect on T cells, yet much remains unknown about the underlying mechanisms that support this effect. The T cell co-stimulatory pathway involving the programmed death-1 (PD-1) receptor and its ligand PD-L1 regulates T cell activation, tolerance, and subsequent immune-mediated tissue damage. In this study, human palatine tonsil-derived MSCs (T-MSCs) constitutively expressed PD-L1 and exhibited a suppressive activity that specifically targeted murine Th17 differentiation. Additionally, polyinosinic–polycytidylic acid (poly I:C), a Toll-like receptor 3 (TLR3) ligand, increased PD-L1 expression on T-MSCs. The elevated PD-L1 levels enhanced the suppressive functions of T-MSCs on Th17 differentiation. Therefore, pre-stimulation of T-MSCs with poly I:C may serve as an effective therapeutic priming step for modulating Th17-dominant immune responses. 相似文献
7.
8.
《Vaccine》2017,35(20):2633-2641
IntroductionThe response rate to hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is low and varies markedly. We performed a systematic review and meta-analysis to determine the response rate to HBV vaccination and identified the factors predictive of an immune response.MethodsWe searched PubMed, Cochrane Library, and Embase databases, and reviewed the titles and abstracts of studies on the efficacy of HBV vaccination in IBD patients performed through July 2016. Anti-HBs levels > 10 IU/L was considered to be an effective immune response. The primary outcome measure was the response rate to HBV vaccination after series completion, and the secondary outcome was identification of factors at baseline predictive of an immune response.ResultsThirteen studies including 1688 patients were eligible for inclusion. Based on a random-effects model, the pooled rate of a response to HBV vaccination among patients with IBD was 61% (95% confidence interval [CI]: 53–69). Young age (mean difference [MD]: −5.7; 95% CI: −8.46, −2.95) and vaccination during disease remission (relative risk [RR]: 1.62; 95% CI: 1.15–2.29) were associated with a positive response to HBV vaccination. In addition, no immunosuppressive therapy was predictive of an immune response compared to immunomodulatory (RR: 1.33; 95% CI: 1.08–1.63) or anti-tumor necrosis factor-α (anti-TNF-α) (RR: 1.57; 95% CI: 1.19–2.08) therapy.ConclusionsBased on this meta-analysis, only three of five IBD patients will show a serological response to HBV vaccination. Vaccination should be performed at the time of IBD diagnosis, during disease remission, or before starting immunosuppressive therapy. 相似文献
10.