全文获取类型
收费全文 | 14609篇 |
免费 | 1236篇 |
国内免费 | 28篇 |
专业分类
耳鼻咽喉 | 75篇 |
儿科学 | 379篇 |
妇产科学 | 227篇 |
基础医学 | 2004篇 |
口腔科学 | 547篇 |
临床医学 | 1497篇 |
内科学 | 3142篇 |
皮肤病学 | 124篇 |
神经病学 | 1406篇 |
特种医学 | 380篇 |
外科学 | 1935篇 |
综合类 | 186篇 |
一般理论 | 19篇 |
预防医学 | 1535篇 |
眼科学 | 282篇 |
药学 | 1324篇 |
中国医学 | 33篇 |
肿瘤学 | 778篇 |
出版年
2023年 | 73篇 |
2022年 | 114篇 |
2021年 | 302篇 |
2020年 | 172篇 |
2019年 | 260篇 |
2018年 | 341篇 |
2017年 | 251篇 |
2016年 | 265篇 |
2015年 | 326篇 |
2014年 | 470篇 |
2013年 | 684篇 |
2012年 | 987篇 |
2011年 | 1005篇 |
2010年 | 554篇 |
2009年 | 547篇 |
2008年 | 866篇 |
2007年 | 911篇 |
2006年 | 886篇 |
2005年 | 897篇 |
2004年 | 874篇 |
2003年 | 737篇 |
2002年 | 808篇 |
2001年 | 216篇 |
2000年 | 182篇 |
1999年 | 246篇 |
1998年 | 160篇 |
1997年 | 155篇 |
1996年 | 118篇 |
1995年 | 117篇 |
1994年 | 93篇 |
1993年 | 93篇 |
1992年 | 138篇 |
1991年 | 128篇 |
1990年 | 119篇 |
1989年 | 126篇 |
1988年 | 115篇 |
1987年 | 99篇 |
1986年 | 107篇 |
1985年 | 102篇 |
1984年 | 109篇 |
1983年 | 107篇 |
1982年 | 104篇 |
1981年 | 99篇 |
1980年 | 60篇 |
1979年 | 80篇 |
1978年 | 55篇 |
1977年 | 54篇 |
1976年 | 53篇 |
1974年 | 48篇 |
1972年 | 41篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
101.
Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons 总被引:5,自引:2,他引:5
David E. Reed Carlos Barajas-Lopez Graeme Cottrell Sara Velazquez-Rocha Olivier Dery Eileen F. Grady Nigel W. Bunnett Stephen J. Vanner 《The Journal of physiology》2003,547(2):531-542
Mast cells that are in close proximity to autonomic and enteric nerves release several mediators that cause neuronal hyperexcitability. This study examined whether mast cell tryptase evokes acute and long-term hyperexcitability in submucosal neurons from the guinea-pig ileum by activating proteinase-activated receptor 2 (PAR2) on these neurons. We detected the expression of PAR2 in the submucosal plexus using RT-PCR. Most submucosal neurons displayed PAR2 immunoreactivity, including those colocalizing VIP. Brief (minutes) application of selective PAR2 agonists, including trypsin, the activating peptide SL-NH2 and mast cell tryptase, evoked depolarizations of the submucosal neurons, as measured with intracellular recording techniques. The membrane potential returned to resting values following washout of agonists, but most neurons were hyperexcitable for the duration of recordings (> 30 min–hours) and exhibited an increased input resistance and amplitude of fast EPSPs. Trypsin, in the presence of soybean trypsin inhibitor, and the reverse sequence of the activating peptide (LR-NH2 ) had no effect on neuronal membrane potential or long-term excitability. Degranulation of mast cells in the presence of antagonists of established excitatory mast cell mediators (histamine, 5-HT, prostaglandins) also caused depolarization, and following washout of antigen, long-term excitation was observed. Mast cell degranulation resulted in the release of proteases, which desensitized neurons to other agonists of PAR2. Our results suggest that proteases from degranulated mast cells cleave PAR2 on submucosal neurons to cause acute and long-term hyperexcitability. This signalling pathway between immune cells and neurons is a previously unrecognized mechanism that could contribute to chronic alterations in visceral function. 相似文献
102.
Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains 总被引:1,自引:0,他引:1
Ma L Chan KW Trendell-Smith NJ Wu A Tian L Lam AC Chan AK Lo CK Chik S Ko KH To CK Kam SK Li XS Yang CH Leung SY Ng MH Stott DI MacPherson GG Huang FP 《European journal of immunology》2005,35(11):3364-3375
Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-gamma and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis. 相似文献
103.
Avilion AA Nicolis SK Pevny LH Perez L Vivian N Lovell-Badge R 《Genes & development》2003,17(1):126-140
104.
Bordetella pertussis Filamentous Hemagglutinin Enhances the Immunogenicity of Liposome-Delivered Antigen Administered Intranasally 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Odile Poulain-Godefroy Nathalie Mielcarek Nathalie Ivanoff Franck Remou Anne-Marie Schacht Nigel Phillips Camille Locht Andr Capron Gilles Riveau 《Infection and immunity》1998,66(4):1764-1767
In an attempt to increase the immunogenicity of mucosally delivered antigens, we incorporated the Bordetella pertussis filamentous hemagglutinin (FHA) adhesin into liposomes containing the glutathione S-transferase of Schistosoma mansoni (Sm28GST) as a model antigen. Outbred mice immunized twice intranasally with liposomes containing a constant suboptimal dose of Sm28GST and increasing doses of FHA produced anti-Sm28GST antibodies in a FHA dose-dependent manner. The addition of 3 μg of FHA to the liposomes induced more than 10-fold-higher anti-Sm28GST antibody titers, compared to those induced by liposomes without FHA. The presence of FHA did not alter the nature of the humoral immune response, and the sera contained anti-Sm28GST immunoglobulin G1 (IgG1), IgG2a, and IgG2b. However, anti-Sm28GST IgA was only detected when at least 3 μg of FHA was added to the preparation. These results show a promising potential for FHA to enhance the immunogenicity of mucosally administered antigens incorporated into liposomes. 相似文献
105.
106.
McManamny P Chy HS Finkelstein DI Craythorn RG Crack PJ Kola I Cheema SS Horne MK Wreford NG O'Bryan MK De Kretser DM Morrison JR 《Human molecular genetics》2002,11(18):2103-2111
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease, caused by the expansion of a trinucleotide repeat (TNR) in exon 1 of the androgen receptor (AR) gene. This disorder is characterized by degeneration of motor and sensory neurons, proximal muscular atrophy, and endocrine abnormalities, such as gynecomastia and reduced fertility. We describe the development of a transgenic model of SBMA expressing a full-length human AR (hAR) cDNA carrying 65 (AR(65)) or 120 CAG repeats (AR(120)), with widespread expression driven by the cytomegalovirus promoter. Mice carrying the AR(120) transgene displayed behavioral and motor dysfunction, while mice carrying 65 CAG repeats showed a mild phenotype. Progressive muscle weakness and atrophy was observed in AR(120) mice and was associated with the loss of alpha-motor neurons in the spinal cord. There was no evidence of neurodegeneration in other brain structures. Motor dysfunction was observed in both male and female animals, showing that in SBMA the polyglutamine repeat expansion causes a dominant gain-of-function mutation in the AR. The male mice displayed a progressive reduction in sperm production consistent with testis defects reported in human patients. These mice represent the first model to reproduce the key features of SBMA, making them a useful resource for characterizing disease progression, and for testing therapeutic strategies for both polyglutamine and motor neuron diseases. 相似文献
107.
Effect of temperature on growth, hemagglutination, and protease activity of Porphyromonas gingivalis
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Percival RS Marsh PD Devine DA Rangarajan M Aduse-Opoku J Shepherd P Curtis MA 《Infection and immunity》1999,67(4):1917-1921
Bacteria persisting in periodontal pockets are exposed to elevated temperatures during periods of inflammation. Temperature is an environmental factor that can modulate gene expression. Consequently, in the present study we examined the effect of temperature on the expression of virulence determinants by the periodontopathogen, Porphyromonas gingivalis. P. gingivalis W50 was grown in a complex medium under hemin excess at pH 7.0 and at a constant temperature of either 37, 39, or 41 degrees C; cultures were monitored for protease and hemagglutinin activity. P. gingivalis grew well at all three temperatures. An increase in growth temperature from 37 to 39 degrees C resulted in a 65% reduction in both total arginine- and lysine-specific activities (P < 0.01). A further rise in growth temperature to 41 degrees C led to even greater reductions in arginine-specific (82%; P < 0.001) and lysine-specific (73%; P < 0. 01) activities. These reductions were also associated with an altered distribution of individual arginine-specific enzyme isoforms. At 41 degrees C, there was a disproportionate reduction in the level of the heterodimeric RI protease, which also contains adhesin domains. The reduction also correlated with a markedly diminished hemagglutination activity of cells, especially in those grown at 41 degrees C, and a reduced immunoreactivity with a monoclonal antibody which recognizes gene products involved in hemagglutination. Thus, as the environmental temperature increased, P. gingivalis adopted a less aggressive phenotype, while retaining cell population levels. The coordinate down-regulation of virulence gene expression in response to an environmental cue linked to the intensity of the host inflammatory response is consistent with the clinically observed cyclical nature of disease progression in periodontal diseases. 相似文献
108.
109.
Mahvash Tavassoli Christiana Ruhrberg Vicky Beaumont Karina Reynolds Nigel Kirkham William P. Collins Farzin Farzaneh 《Genes, chromosomes & cancer》1993,8(3):195-198
Chromosomal deletions, associated with the loss of normal function of tumour suppressor genes, have been identified in a variety of both familial and sporadic human cancers. Although the molecular pathology of ovarian cancer is not understood, several studies have reported deletions in chromosome 17 in ovarian tumours. We have used 13 restriction site polymorphic, microsatellite, and variable number tandem repeat markers to make a detailed analysis of chromosome 17 deletions in 12 benign and 19 malignant ovarian tumours. Two benign and 11 malignant tumours were informative for at least one marker on each arm of the chromosome. Loss of heterozygosity (LOH) was detected in both arms (by all informative markers) in 5 malignant tumours from four women (three with the disease at FIGO stage la). In a further bilateral ovarian tumour a partial LOH affecting 17q22-q25 was present in one ovary only. By contrast to a number of previous studies, none of the 19 malignant and 12 benign tumours showed ERBB2 (17q12ndash;22) amplification. The data presented show that the loss of a whole copy of chromosome 17 is a frequent and relatively early event in the development of some ovarian cancers. This suggests the possible involvement of multiple chromosome 17 loci in the pathogenesis of ovarian cancer. Equally plausible is that the loss of a whole chromosome copy could be the product of chromosomal instabilities induced by loss of the normal allele of tumour suppressors, such as TP53, located on this chromosome. © 1993 Wiley-Liss, Inc. 相似文献
110.