全文获取类型
收费全文 | 5961篇 |
免费 | 629篇 |
国内免费 | 254篇 |
专业分类
耳鼻咽喉 | 37篇 |
儿科学 | 116篇 |
妇产科学 | 95篇 |
基础医学 | 1087篇 |
口腔科学 | 130篇 |
临床医学 | 406篇 |
内科学 | 1132篇 |
皮肤病学 | 135篇 |
神经病学 | 618篇 |
特种医学 | 100篇 |
外科学 | 605篇 |
综合类 | 714篇 |
现状与发展 | 1篇 |
预防医学 | 170篇 |
眼科学 | 110篇 |
药学 | 773篇 |
1篇 | |
中国医学 | 152篇 |
肿瘤学 | 462篇 |
出版年
2024年 | 6篇 |
2023年 | 74篇 |
2022年 | 118篇 |
2021年 | 158篇 |
2020年 | 170篇 |
2019年 | 241篇 |
2018年 | 207篇 |
2017年 | 227篇 |
2016年 | 273篇 |
2015年 | 286篇 |
2014年 | 440篇 |
2013年 | 481篇 |
2012年 | 403篇 |
2011年 | 396篇 |
2010年 | 334篇 |
2009年 | 308篇 |
2008年 | 306篇 |
2007年 | 316篇 |
2006年 | 274篇 |
2005年 | 230篇 |
2004年 | 177篇 |
2003年 | 197篇 |
2002年 | 179篇 |
2001年 | 127篇 |
2000年 | 126篇 |
1999年 | 100篇 |
1998年 | 73篇 |
1997年 | 78篇 |
1996年 | 63篇 |
1995年 | 64篇 |
1994年 | 51篇 |
1993年 | 41篇 |
1992年 | 42篇 |
1991年 | 56篇 |
1990年 | 29篇 |
1989年 | 20篇 |
1988年 | 21篇 |
1987年 | 20篇 |
1986年 | 11篇 |
1985年 | 25篇 |
1984年 | 15篇 |
1983年 | 11篇 |
1982年 | 13篇 |
1981年 | 9篇 |
1980年 | 11篇 |
1979年 | 9篇 |
1978年 | 4篇 |
1977年 | 7篇 |
1976年 | 9篇 |
1974年 | 3篇 |
排序方式: 共有6844条查询结果,搜索用时 15 毫秒
1.
《Vaccine》2022,40(11):1594-1605
In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes. 相似文献
2.
《Vaccine》2019,37(31):4382-4391
Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8+ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα+ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice. 相似文献
3.
4.
5.
对13例体外循环病人进行了观察,发现体外循环后TXB2/6-keto-PGF1α显著增高,表明体外循环使血小板受损,而血小板受损是体外循环后失血的主要原因之一。 相似文献
6.
短串联重复序列HumFGA、D3S1359的法医学应用研究 总被引:1,自引:0,他引:1
对短串联重复序列(short tandem repeats,STR)的两个高多态位点HumFGA(human alpha fibrinogen,人类α-纤维蛋白原基因)、D3S1359的法医学应用进行研究,并通过实际检测案件统计结果进行评估。实验结果表明:两位点灵敏度高,分别为0.2、0.5ngDNA;同一性和可重复性均较理想;种属特异性好,常见动物未发现扩增产物,仅灵长类动物(黑叶猴和猕猴)有扩增条带;复合扩增体系效果良好;在352次减数分裂中,D3S1359未发现突变,HumFGA检测到1次,突变率为0.28%;实际案件统计和应用结果也显示两位点是多态性高,实用性强的两个遗传标记系统。HumFGA和D3S1359在法医学个人识别与亲子鉴定案例中有较大应用价值。 相似文献
7.
'Gliosarcomas' have long been considered to be mixed gliomas and sarcomas. The present study failed to define criteria which clearly delineate 'gliosarcomas' from glioblastoma multiforme and suggests that 'gliosarcomas' should be considered as spindle cell glioblastomas. A total of six cases originally diagnosed as 'gliosarcomas' were compared with four cases of glioblastoma multiforme. No clinical or prognostic features were defined which would clearly separate 'gliosarcomas' from glioblastoma multiforme. Macroscopically, biopsies from 'gliosarcomas' ranged from firm, apparently well-circumscribed tumours to poorly circumscribed lesions with a soft consistency resembling glioblastoma multiforme. Histology revealed a continuous spectrum in which 'gliosarcomas' with large reticulin-rich areas of spindle cells merged with typical glioblastomas containing only small islands of spindle cells and reticulin staining. Immunocytochemistry for glial fibrillary acidic protein (GFAP); S100 protein and alpha-smooth muscle actin (ASMA) showed that the majority of cells in reticulin-poor areas of 'gliosarcoma' and glioblastomas expressed S100 protein and GFAP; many expressed ASMA and some expressed both GFAP and ASMA. Spindle cells in reticulin-rich areas of 'gliosarcomas' and glioblastomas most frequently expressed ASMA but many cells also expressed S100 protein and GFAP; some cells expressed both GFAP and ASMA. The results of this study and a review of the literature suggests that there is a clinical, radiological and pathological continuum with glioblastoma and 'gliosarcoma' at different ends of the spectrum. It is suggested, therefore, that most, if not all, 'gliosarcomas' be redesignated as spindle cell glioblastomas and not be considered as a mixture of glioma and sarcoma. 相似文献
8.
缺氧诱导因子-lα(hypoxia-inducible factor-1alpha,HIF-lα)是近来发现的广泛存在于哺乳动物和人体内的一种缺氧应答调控因子,在调节缺氧诱导的基因表达中起关键性作用。它可调节表达多种靶基因如血管内皮生长因子、促红细胞生成素等,对改善脑缺氧缺血后能量代谢障碍、促进脑血流动力学恢复、抑制兴奋性氨基酸毒性、减少细胞凋亡等起重要作用。通过进一步对HIF-lα及其靶基因的研究,可能为临床治疗脑缺氧缺血性损伤提供了一种新的治疗策略。 相似文献
9.
1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence. 相似文献
10.
目的:研究重组人内皮细胞衍生的白细胞介素-8(IL8)对失血性休克的作用.方法:大鼠股动脉放血至MABP532kPa,维持90min,复制晚期失血性休克模型.输血后,静脉注射IL8250μg·kg-1.放免法测定血浆ET1和6KPGF1α含量.结果:给予IL8后,MABP显著提高,休克状态改善,2h存活率相应提高;休克晚期血浆ET1水平比正常明显升高(21±4vs82±18ng·L-1,P<001),血浆6KPGF1α含量明显降低(107±12vs157±11ng·L-1,P<001).IL8显著降低血浆ET1水平(10±4ng·L-1,P<001),提高血浆6KPGF1α含量(368±16ng·L-1,P<001).结论:IL8具有较好的抗休克作用. 相似文献