全文获取类型
收费全文 | 8364篇 |
免费 | 579篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 86篇 |
儿科学 | 277篇 |
妇产科学 | 176篇 |
基础医学 | 1164篇 |
口腔科学 | 88篇 |
临床医学 | 1103篇 |
内科学 | 1570篇 |
皮肤病学 | 197篇 |
神经病学 | 782篇 |
特种医学 | 305篇 |
外科学 | 885篇 |
综合类 | 43篇 |
一般理论 | 5篇 |
预防医学 | 897篇 |
眼科学 | 234篇 |
药学 | 482篇 |
中国医学 | 13篇 |
肿瘤学 | 649篇 |
出版年
2023年 | 66篇 |
2022年 | 106篇 |
2021年 | 214篇 |
2020年 | 162篇 |
2019年 | 232篇 |
2018年 | 282篇 |
2017年 | 231篇 |
2016年 | 179篇 |
2015年 | 217篇 |
2014年 | 281篇 |
2013年 | 429篇 |
2012年 | 662篇 |
2011年 | 657篇 |
2010年 | 354篇 |
2009年 | 332篇 |
2008年 | 556篇 |
2007年 | 536篇 |
2006年 | 510篇 |
2005年 | 486篇 |
2004年 | 469篇 |
2003年 | 409篇 |
2002年 | 360篇 |
2001年 | 113篇 |
2000年 | 90篇 |
1999年 | 97篇 |
1998年 | 86篇 |
1997年 | 60篇 |
1996年 | 50篇 |
1995年 | 35篇 |
1994年 | 30篇 |
1993年 | 33篇 |
1992年 | 41篇 |
1991年 | 35篇 |
1990年 | 29篇 |
1989年 | 46篇 |
1988年 | 26篇 |
1987年 | 39篇 |
1986年 | 28篇 |
1985年 | 36篇 |
1984年 | 36篇 |
1983年 | 28篇 |
1982年 | 25篇 |
1981年 | 37篇 |
1980年 | 20篇 |
1979年 | 29篇 |
1977年 | 12篇 |
1976年 | 14篇 |
1975年 | 15篇 |
1974年 | 16篇 |
1966年 | 14篇 |
排序方式: 共有8956条查询结果,搜索用时 15 毫秒
31.
Variations in Helicobacter pylori lipopolysaccharide to evade the innate immune component surfactant protein D 总被引:2,自引:0,他引:2
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)
Khamri W Moran AP Worku ML Karim QN Walker MM Annuk H Ferris JA Appelmelk BJ Eggleton P Reid KB Thursz MR 《Infection and immunity》2005,73(11):7677-7686
Helicobacter pylori is a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregating H. pylori. Wide variation in the SP-D binding affinity to H. pylori has been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show that H. pylori evades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P = 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen. 相似文献
32.
PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. 总被引:9,自引:0,他引:9
Delin Ren Trevor N Collingwood Edward J Rebar Alan P Wolffe Heidi S Camp 《Genes & development》2002,16(1):27-32
To determine functional differences between the two splice variants of PPARgamma (gamma1 and gamma2), we sought to selectively repress gamma2 expression by targeting engineered zinc finger repressor proteins (ZFPs) to the gamma2-specific promoter, P2. In 3T3-L1 cells, expression of ZFP55 resulted in >50% reduction in gamma2 expression but had no effect on gamma1, whereas adipogenesis was similarly reduced by 50%. However, ZFP54 virtually abolished both gamma2 and gamma1 expression, and completely blocked adipogenesis. Overexpression of exogenous gamma2 in the ZFP54-expressing cells completely restored adipogenesis, whereas overexpression of gamma1 had no effect. This finding clearly identifies a unique role for the PPARgamma2 isoform. 相似文献
33.
Expression of CD44 in effusions of patients diagnosed with serous ovarian carcinoma – diagnostic and prognostic implications 总被引:2,自引:0,他引:2
Berner HS Davidson B Berner A Risberg B Kristensen GB Trope CG Van de Putte G Nesland JM 《Clinical & experimental metastasis》2000,18(2):197-202
CD44 is a family of cell adhesion molecules involved in a variety of cellular functions. The present study analysed the expression
of two CD44 isoforms in serous effusions of patients diagnosed with ovarian carcinoma and corresponding primary and metastatic
lesions. Fifty-eight effusions, 23 primary ovarian tumours, and 44 metastatic lesions were studied for protein expression
of CD44s and v3-10 using immunohistochemistry. Results were correlated with clinical parameters. CD44v3-10 was seen in carcinoma
cells in the majority of cases at all sites. Malignant effusions showed an up-regulation of CD44s compared to both primary
tumours and metastatic solid lesions. Mesothelial cells frequently expressed CD44s, but were rarely immunoreactive for v3-10.
CD44s immunoreactivity in cancer cells in effusions was significantly more often observed in patients with FIGO stage 3 than
in stage 4 patients (P = 0.045). Staining results did not correlate with age, effusion site, metastatic site, tumour grade or residual tumour mass
after initial surgery. Likewise, comparison of overall and disease-free survival with expression of the CD44 isoforms studied
did not reveal any statistically significant associations. The up-regulation in CD44 levels in effusions, primarily in stage
3 disease, suggests that adhesion of ovarian carcinoma cells to mesothelium may be regulated at the level of CD44s expression,
and provides further evidence of phenotypic alteration in the transition from primary tumour cell clones to effusions. The
similar expression profile of CD44 in carcinoma cells in peritoneal and pleural effusions supports our previous observations
and the hypothesis that carcinoma cells in peritoneal effusions are truly metastatic.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
34.
Heidi L. Weiss Santosh Niwas William E. Grizzle Chandrika Piyathilake 《Disease markers》2004,19(6):273-278
The role of biomarkers in disease prognosis continues to be an important investigation in many cancer studies. In order for these biomarkers to have practical application in clinical decision making regarding patient treatment and follow-up, it is common to dichotomize patients into those with low vs. high expression levels. In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of the ROC, sensitivity, specificity, as well as likelihood ratios were calculated to determine levels of growth factor biomarkers that best differentiate lung cancer cases versus control subjects. Selected cut-off points for p185erbB-2 and EGFR membrane appear to have good discriminating power to differentiate control tissues versus uninvolved tissues from patients with lung cancer (AUC = 89% and 90%, respectively); while AUC increased to at least 90% for selected cut-off points for p185erbB-2 membrane, EGFR membrane, and FASE when comparing between control versus carcinoma tissues from lung cancer cases. Using data from control subjects compared to patients with lung cancer, we presented a simple and intuitive approach to determine dichotomized levels of biomarkers and validated the value of these biomarkers as surrogate endpoints for cancer outcome. 相似文献
35.
Adenoviral vectors expressing siRNAs for discovery and validation of gene function 总被引:5,自引:0,他引:5
下载免费PDF全文
![点击此处可从《Genome research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Arts GJ Langemeijer E Tissingh R Ma L Pavliska H Dokic K Dooijes R Mesić E Clasen R Michiels F van der Schueren J Lambrecht M Herman S Brys R Thys K Hoffmann M Tomme P van Es H 《Genome research》2003,13(10):2325-2332
RNA interference is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types. In mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing these siRNAs, have been used to down-modulate gene expression. However, inefficient transfection protocols, in particular, for primary cell types, have hampered the use of these tools in disease-relevant cellular assays. To be able to use this technology for genome-wide function screening, a more robust transduction protocol, resulting in a longer duration of the knock-down effect, is required. Here, we describe the validation of adenoviral vectors that express hairpin RNAs that are further processed to siRNAs. Infection of cell lines, or primary human cells, with these viruses leads to an efficient, sequence-specific, and prolonged reduction of the corresponding target mRNA, resulting in a reduction of the encoded protein level in the cell. For knock-down of one of the targets, GalphaS, we have measured inhibition of ligand-dependent, G-protein-coupled signaling. It is expected that this technology will prove to be of great value in target validation and target discovery efforts. 相似文献
36.
37.
McCarty MF Bielenberg D Donawho C Bucana CD Fidler IJ 《Clinical & experimental metastasis》2002,19(7):609-615
Primary tumor growth and metastasis depend on angiogenesis, which is determined by the balance between proangiogenic and antiangiogenic
molecules. Interferon (IFN)-α and -β inhibit angiogenesis through downregulation of interleukin-8, matrix metalloproteinase-9,
and basic fibroblast growth factor. To provide evidence for the causal role of IFN-α/β in the induction of neoplasms, their
angiogenesis, and hence, progressive growth, we carried out experiments using 129S6 IFN-α/β receptor −/− mice back-crossed
to BALB/c nude mice. Subcutaneous angiogenesis was determined following implantation of gelfoam sponges containing 0.4% agarose
and several proangiogenic molecules. Tumorigenicity and production of lung metastasis were determined subsequent to subcutaneous
and intravenous injections, respectively, of highly metastatic A375SM human melanoma cells. Carcinogenesis was induced by
chronic exposure of mice to UVB radiation (5 kJ/m2, 3 times/week). Angiogenesis, tumorigenicity, and production of metastasis, as well as development of autochthonous skin
tumors, were all accelerated in IFN-α/β receptor −/− mice as compared to control mice. Collectively, the data show that inability
to respond to endogenous IFN-α/β (through a mutation in the IFN-α/β receptor) leads to increased susceptibility to carcinogenesis,
enhanced angiogenesis, tumorigenicity, and metastasis.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
38.
Steffen Dietzel Anna Jauch Dirk Kienle Guoquiong Qu Heidi Holtgreve-Grez Roland Eils Christian Munkel Michael Bittner Paul S. Meltzer Jeffrey M. Trent Thomas Cremer 《Chromosome research》1998,6(1):25-33
Fluorescence in situ hybridization (FISH) with microdissection probes from human chromosomes 3 and 6 was applied to visualize arm and subregional band domains in human amniotic fluid cell nuclei. Confocal laser scanning microscopy and quantitative three-dimensional image analysis showed a pronounced variability of p- and q-arm domain arrangements and shapes. Apparent intermingling of neighbouring arm domains was limited to the domain surface. Three-dimensional distance measurements with pter and qter probes supported a high variability of chromosome territory folding. 相似文献
39.
Flow Perfusion Culture of Marrow Stromal Cells Seeded on Porous Biphasic Calcium Phosphate Ceramics 总被引:2,自引:0,他引:2
Holtorf HL Sheffield TL Ambrose CG Jansen JA Mikos AG 《Annals of biomedical engineering》2005,33(9):1238-1248
Calcium phosphate ceramics have been widely used for filling bone defects to aid in the regeneration of new bone tissue. Addition of osteogenic cells to porous ceramic scaffolds may accelerate the bone repair process. This study demonstrates the feasibility of culturing marrow stromal cells (MSCs) on porous biphasic calcium phosphate ceramic scaffolds in a flow perfusion bioreactor. The flow of medium through the scaffold porosity benefits cell differentiation by enhancing nutrient transport to the scaffold interior and by providing mechanical stimulation to cells in the form of fluid shear. Primary rat MSCs were seeded onto porous ceramic (60% hydroxyapatite, 40% β-tricalcium phosphate) scaffolds, cultured for up to 16 days in static or flow perfusion conditions, and assessed for osteoblastic differentiation. Cells were distributed throughout the entire scaffold by 16 days of flow perfusion culture whereas they were located only along the scaffold perimeter in static culture. At all culture times, flow perfused constructs demonstrated greater osteoblastic differentiation than statically cultured constructs as evidenced by alkaline phosphatase activity, osteopontin secretion into the culture medium, and histological evaluation. These results demonstrate the feasibility and benefit of culturing cell/ceramic constructs in a flow perfusion bioreactor for bone tissue engineering applications. 相似文献
40.
David W. Barbara William D. Edwards Heidi M. Connolly Joseph A. Dearani 《Cardiovascular pathology》2008,17(3):166-171
BACKGROUND: Ebstein's anomaly has been described extensively in autopsy material. However, there have been no large surgical pathology series of this malformation. OBJECTIVE: To review clinical and surgical pathologic features of a large number of cases of Ebstein's anomaly from a single institution. METHODS: Review of medical histories, surgical reports, and surgical pathology reports at the Mayo Clinic (2000-2005). RESULTS: Among 104 patients, the mean age was 31 years (2 months-79 years), and 57% were female. Common ECG abnormalities included right bundle branch block (58%), first-degree heart block (31%), preexcitation (18%), and nonspecific intraventricular conduction delay/block (15%). Moreover, 74% had inter-atrial communication, 13% mitral valve prolapse, and 5% bicuspid aortic valve. Clinically, all had tricuspid regurgitation (severe in 74%), and 17% of anterior leaflets were fenestrated. No tricuspid valve was calcified. Surgically, tricuspid tissue was removed during replacement in 99% and repair in 1%. The anterior tricuspid leaflet was resected in 98%, and its length was 0.81-9.3 cm/m2 body surface area (mean, 3.3). Characteristically, leaflets were large and had irregular shapes and numerous short cordal or direct myocardial insertions. One tricuspid valve had two papillary fibroelastomas. None had clinical or pathologic evidence of active or healed endocarditis. CONCLUSIONS: Among patients with Ebstein's malformation, tricuspid valve tissue almost exclusively was removed during valve replacement and represented the anterior leaflet. Valve tissue was generally large, irregularly shaped, and associated with insertion of short cords or myocardial stumps. Interestingly, although appreciably deformed, Ebstein valves were not associated with infective endocarditis. 相似文献