全文获取类型
收费全文 | 12269篇 |
免费 | 852篇 |
国内免费 | 118篇 |
专业分类
耳鼻咽喉 | 115篇 |
儿科学 | 281篇 |
妇产科学 | 436篇 |
基础医学 | 1594篇 |
口腔科学 | 406篇 |
临床医学 | 1119篇 |
内科学 | 2638篇 |
皮肤病学 | 213篇 |
神经病学 | 937篇 |
特种医学 | 565篇 |
外国民族医学 | 3篇 |
外科学 | 1932篇 |
综合类 | 366篇 |
一般理论 | 4篇 |
预防医学 | 633篇 |
眼科学 | 114篇 |
药学 | 656篇 |
2篇 | |
中国医学 | 47篇 |
肿瘤学 | 1178篇 |
出版年
2023年 | 78篇 |
2022年 | 121篇 |
2021年 | 347篇 |
2020年 | 188篇 |
2019年 | 254篇 |
2018年 | 324篇 |
2017年 | 227篇 |
2016年 | 270篇 |
2015年 | 306篇 |
2014年 | 395篇 |
2013年 | 512篇 |
2012年 | 838篇 |
2011年 | 812篇 |
2010年 | 464篇 |
2009年 | 411篇 |
2008年 | 677篇 |
2007年 | 750篇 |
2006年 | 617篇 |
2005年 | 625篇 |
2004年 | 612篇 |
2003年 | 522篇 |
2002年 | 522篇 |
2001年 | 354篇 |
2000年 | 351篇 |
1999年 | 350篇 |
1998年 | 149篇 |
1997年 | 150篇 |
1996年 | 117篇 |
1995年 | 90篇 |
1994年 | 98篇 |
1993年 | 83篇 |
1992年 | 173篇 |
1991年 | 160篇 |
1990年 | 130篇 |
1989年 | 166篇 |
1988年 | 95篇 |
1987年 | 133篇 |
1986年 | 101篇 |
1985年 | 73篇 |
1984年 | 72篇 |
1983年 | 47篇 |
1982年 | 43篇 |
1981年 | 39篇 |
1980年 | 38篇 |
1979年 | 48篇 |
1978年 | 27篇 |
1977年 | 28篇 |
1976年 | 39篇 |
1975年 | 29篇 |
1974年 | 30篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
Saulot V Vittecoq O Salle V Drouot L Legoedec J Le Loët X Godin M Ducroix JP Ménard JF Tron F Gilbert D 《Journal of autoimmunity》2002,19(1-2):55-61
To identify new autoantibody populations in patients with rheumatic diseases, a cDNA expression library was immunoscreened with a rheumatoid arthritis (RA) patient's serum which contains autoantibodies binding to uncharacterized polypeptides by Western-blotting. One clone encoding the amino-terminal region (Nt) [domain L and half of domain I] of human calpastatin was selected. Different fragments of the selected cDNA were prepared and the corresponding recombinant polypeptides were produced by in vitro translation and analysed by Western blotting. Most RA sera bound to recombinant amino-terminal region and domain I but not to domain L. This prompted us to use a recombinant polypeptide corresponding to the domain I of calpastatin as the antigen in a solid-phase ELISA to test sera from patients with various systemic rheumatic diseases and healthy controls.Anti-calpastatin domain I antibodies (ACAST-DI Ab), were detected by ELISA in RA, systemic lupus erythematosus (SLE), Sj?gren's syndrome and control sera at respective frequencies of 10, 9, 0 and 1%. These Ab did not have prognostic value in early RA; high levels were significantly associated with vasculitis in SLE. Antibodies reacting with the calpastatin amino-terminal region are produced during systemic rheumatic diseases and are predominantly directed against domain I. High levels of these Ab may constitute a marker of vasculitis in SLE. 相似文献
82.
Extensive homology between the leukotoxin of Pasteurella haemolytica A1 and the alpha-hemolysin of Escherichia coli. 总被引:18,自引:21,他引:18 下载免费PDF全文
The 19.8- and 101.9-kilodalton leukotoxin proteins of Pasteurella haemolytica (LKTC and LKTA, respectively) share extensive homology with the HLYC and HLYA alpha-hemolysin proteins of Escherichia coli. The leukotoxin LKTA protein cross-reacts with hemolysin-specific antisera in Western blot (immunoblot) analysis, indicating that it shares epitopes with the alpha-hemolysin HLYA protein. Both LKTA and HLYA contain a conserved hydrophobic region, as well as a set of tandemly repeated domains. These features have been implicated in the lytic function of the alpha-hemolysin. 相似文献
83.
The first clinical isolate of Legionella parisiensis, from a liver transplant patient with pneumonia. 总被引:1,自引:0,他引:1 下载免费PDF全文
F Lo Presti S Riffard F Vandenesch M Reyrolle E Ronco P Ichai J Etienne 《Journal of clinical microbiology》1997,35(7):1706-1709
A bluish white autofluorescent strain of Legionella was isolated from the tracheal aspirate of a female liver transplant patient who developed hospital-acquired pneumonia. This strain had biochemical characteristics compatible with those of L. cherrii, L. anisa, and L. parisiensis and could not be differentiated from L. bozemanii and L. parisiensis by the direct fluorescent-antibody assay. Phylogenetic analysis of partial 16S rRNA gene sequences of this strain (ATCC 700174) revealed the closest homology to the species L. parisiensis (99.5%). An L. parisiensis species-specific profile was also identified by a random amplified polymorphic DNA technique. This is the first report of L. parisiensis isolation from humans. 相似文献
84.
Chia-Ying Liu Chih-Cheng Lai Hsiu-Tzy Chiang Min-Chi Lu Ling-Fang Wang Tsai-Ling Tsai Mei-Yu Kang Yi-Ni Jan Yi-Ting Lo Wen-Chien Ko Shu-Hui Tseng Chun-Ming Lee Po-Ren Hsueh 《Journal of microbiology, immunology, and infection》2019,52(1):62-74
Background/purpose
This study investigated the distribution and persistence of multidrug resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and multidrug-resistant Acinetobacter baumannii (MDRAB) in six long-term care facilities (LTCFs).Methods
We investigated the distribution of MDROs in residents of six LTCFs and their environments from January to December 2016 (intervention period). Active surveillance of colonization of MDROs was performed by culturing rectal and nasal swab samples from the residents every three months. Multilocus sequence typing (MLST) was conducted, and genes for panton-valentine leukocidin (PVL) from MRSA isolates were determined.Results
A total of 521 samples were positive for MDROs, and MRSA was the most common organism (65.1%), followed by MDRAB (11.3%), carbapenem-resistant Klebsiella pneumoniae (11.1%), carbapenem-resistant Escherichia coli (4.6%), and carbapenem-resistant P. aeruginosa (2.1%, n = 11). By a linear regression model, positive MRSA isolates from the environment were found to be statistically significant and associated with the number of colonized LTCF residents (p = 0.01), while the timing of the surveillance culture was not (p = 0.227). The main MLST types associated with PVL-production were sequence type (ST) 59, (40.0%, 24/60), ST30 (21.4%, 3/14), ST8 (87.5%, 14/16), and ST45 (3.6%, 1/28). The susceptibility rates of tetracycline (96.7%), trimethoprim-sulfamethoxazole (96.7%), and ciprofloxacin (81.7%) were statistically significant and higher in MRSA ST59, compared to the rates in MRSA ST45 isolates.Conclusions
MRSA was the most commonly colonized MDRO, both in the LTCF residents and in the environment, followed by MDRAB and carbapenem-resistant K. pneumoniae. 相似文献85.
Gaëlle Dzangué-Tchoupou Kuberaka Mariampillai Loïs Bolko Damien Amelin Wladimir Mauhin Aurélien Corneau Catherine Blanc Yves Allenbach Olivier Benveniste 《Autoimmunity reviews》2019,18(4):325-333
Background
Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.Objectives
Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.Methods
Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).Results
Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.Conclusion
Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease. 相似文献86.
Detection and Identification of Actinobacillus pleuropneumoniae Serotype 5 by Multiplex PCR 总被引:9,自引:0,他引:9 下载免费PDF全文
Terry M. Lo Christine K. Ward Thomas J. Inzana 《Journal of clinical microbiology》1998,36(6):1704-1710
Serotyping of Actinobacillus pleuropneumoniae is based on detection of the serotype-specific capsular antigen. However, not all isolates can be serotyped, and some may cross-react with multiple serotyping reagents. To improve sensitivity and specificity of serotyping and for early detection, a multiplex PCR assay was developed for detection of A. pleuropneumoniae and identification of serotype 5 isolates. DNA sequences specific to the conserved export and serotype-specific biosynthesis regions of the capsular polysaccharide of A. pleuropneumoniae serotype 5 were used as primers to amplify 0.7- and 1.1-kb DNA fragments, respectively. The 0.7-kb fragment was amplified from all strains of A. pleuropneumoniae tested with the exception of serotype 4. The 0.7-kb fragment was not amplified from any heterologous species that are also common pathogens or commensals of swine. In contrast, the 1.1-kb fragment was amplified from all serotype 5 strains only. The assay was capable of amplifying DNA from less than 102 CFU. The A. pleuropneumoniae serotype 5 capsular DNA products were readily amplified from lung tissues obtained from infected swine, although the 1.1-kb product was not amplified from some tissues stored frozen for 6 years. The multiplex PCR assay enabled us to detect A. pleuropneumoniae rapidly and to distinguish serotype 5 strains from other serotypes. The use of primers specific to the biosynthesis regions of other A. pleuropneumoniae serotypes would expand the diagnostic and epidemiologic capabilities of this assay. 相似文献
87.
Expression of sialyl-Lewis X, an E-selectin ligand, in inflammation, immune processes, and lymphoid tissues. 总被引:1,自引:0,他引:1 下载免费PDF全文
J. M. Munro S. K. Lo C. Corless M. J. Robertson N. C. Lee R. L. Barnhill D. S. Weinberg M. P. Bevilacqua 《The American journal of pathology》1992,141(6):1397-1408
The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined. 相似文献
88.
Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization 总被引:15,自引:0,他引:15
Hui AB Lo KW Yin XL Poon WS Ng HK 《Laboratory investigation; a journal of technical methods and pathology》2001,81(5):717-723
We have used a new method of genomic microarray to investigate amplification of oncogenes throughout the genome of glioblastoma multiforme (GBM). Array-based comparative genomic hybridization (array CGH) allows for simultaneous examination of 58 oncogenes/amplicons that are commonly amplified in various human cancers. Amplification of multiple oncogenes in human cancers can be rapidly determined in a single experiment. Tumor DNA and normal control DNA were labeled by nick translation with green- and red-tagged nucleotides, respectively. Instead of hybridizing to normal metaphase chromosomes in conventional comparative genomic hybridization (CGH), the probes of the mixed fluorescent labeled DNA were applied to genomic array templates comprised of P1, PAC, and BAC clones of 58 target oncogenes. The baseline for measuring deviations was established by performing a series of independent array CGH using test and reference DNA made from normal individuals. In the present study, we examined fourteen GBMs (seven cell lines and seven tumours) with CGH and array CGH to reveal the particular oncogenes associated with this cancer. High-level amplifications were identified on the oncogenes/amplicons CDK4, GLI, MYCN, MYC, MDM2, and PDGFRA. The highest frequencies of gains were detected on PIK3CA (64.3%), EGFR (57.1%), CSE1L (57.1%), NRAS (50%), MYCN (42.9%), FGR (35.7%), ESR (35.7%), PGY1 (35.7%), and D17S167 (35.7%). These genes are suggested to be involved in the GBM tumorigenesis. 相似文献
89.
Thirty seven cases of oesophageal squamous cell carcinoma were studied by applying DNA slot blot analysis and in situ hybridisation using type specific probes for HPV 6, 11, 16 and 18. Cases of condyloma accuminata, cervical carcinoma, and laryngeal papilloma were used as controls. Blocks including areas of invasive carcinoma, intraepithelial neoplasia, and normal epithelium were studied in each case. No HPV genome was detectable in any of the oesophageal cases. It is concluded that these types of HPV do not have an association with oesophageal squamous cell carcinoma. 相似文献
90.
B J Zheng S K Lo J S Tam M Lo C Y Yeung M H Ng 《Journal of clinical microbiology》1989,27(9):2083-2090
We determined titers of group A rotavirus common antibodies and neutralizing antibodies against serotypes 1 to 4 of prototype human rotavirus (HRV) in cord blood and serum specimens obtained from 38 infants at 4-month intervals from birth until 2 years of age. Nineteen of the infants developed one episode of HRV diarrhea each, and they were matched by age and birth weight with the other 19 infants, who did not develop HRV diarrhea during the follow-up period. We estimated the incidence rate of HRV infection for the two groups of infants combined to be a minimum of 1.34 episodes per infant per year, which is 22 times more common than the occurrence of overt disease caused by the virus in this community. The infection occurred constantly throughout the first 2 years of infancy, whereas all but one of the 19 episodes of overt disease occurred before 12 months of age. Seven of these overt episodes were preceded by at least one episode of subclinical infection earlier, and the other seven were probably due to primary HRV infection. The remaining five episodes occurred before 4 months of age, so that we could not ascertain whether they were due to primary infections because of the presence of maternal antibodies. We showed that levels of HRV antibodies in serum specimens obtained before clinical onset of diarrhea varied widely, and, for most infants in the diarrheal group, levels of these antibodies were similar to those in the serum specimens obtained at the same times from the corresponding age- and birth weight-matched control infants. Nevertheless, the age at which overt disease caused by HRV was most prevalent coincided with the time when the maternal antibodies had declined to low levels but the infants had not yet acquired high titers of these antibodies in their sera. 相似文献