全文获取类型
收费全文 | 7685篇 |
免费 | 463篇 |
国内免费 | 43篇 |
专业分类
耳鼻咽喉 | 46篇 |
儿科学 | 111篇 |
妇产科学 | 128篇 |
基础医学 | 1123篇 |
口腔科学 | 286篇 |
临床医学 | 707篇 |
内科学 | 1677篇 |
皮肤病学 | 379篇 |
神经病学 | 940篇 |
特种医学 | 406篇 |
外科学 | 983篇 |
综合类 | 34篇 |
预防医学 | 300篇 |
眼科学 | 124篇 |
药学 | 462篇 |
中国医学 | 2篇 |
肿瘤学 | 483篇 |
出版年
2024年 | 3篇 |
2023年 | 41篇 |
2022年 | 80篇 |
2021年 | 181篇 |
2020年 | 141篇 |
2019年 | 140篇 |
2018年 | 149篇 |
2017年 | 132篇 |
2016年 | 204篇 |
2015年 | 222篇 |
2014年 | 280篇 |
2013年 | 354篇 |
2012年 | 629篇 |
2011年 | 595篇 |
2010年 | 378篇 |
2009年 | 346篇 |
2008年 | 606篇 |
2007年 | 598篇 |
2006年 | 574篇 |
2005年 | 558篇 |
2004年 | 473篇 |
2003年 | 421篇 |
2002年 | 429篇 |
2001年 | 81篇 |
2000年 | 44篇 |
1999年 | 84篇 |
1998年 | 95篇 |
1997年 | 74篇 |
1996年 | 42篇 |
1995年 | 40篇 |
1994年 | 26篇 |
1993年 | 30篇 |
1992年 | 15篇 |
1991年 | 21篇 |
1990年 | 14篇 |
1989年 | 8篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 8篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 8篇 |
1979年 | 3篇 |
1976年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1969年 | 4篇 |
1958年 | 2篇 |
排序方式: 共有8191条查询结果,搜索用时 0 毫秒
21.
22.
Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia. 相似文献
23.
Sylvia Czapla Ralf Ruhmann Joachim Rübner Veit Zschuppe Dietmar Wolff 《Macromolecular chemistry and physics.》1993,194(1):243-250
The synthesis and characterization of new poly({6-[4-(4-cyanophenylcarbamoyl)phenoxy]hexyl methacrylate}-co-{6-[4-(4- cyanophenylazo)phenoxy]hexyl methacrylate}) are reported. Their liquid-crystalline properties are investigated using differential scanning calorimetry, polarizing microscopy and X-ray diffraction techniques. The glass transition temperatures and the clearing points can be influenced by variation of the copolymer composition. The substances offer a relatively broad temperature range of mesomorphic properties suitable for photochemical studies. 相似文献
24.
25.
The effect of surface chemistry modification of titanium alloy on signalling pathways in human osteoblasts 总被引:2,自引:0,他引:2
Zreiqat H Valenzuela SM Nissan BB Roest R Knabe C Radlanski RJ Renz H Evans PJ 《Biomaterials》2005,26(36):7579-7586
Establishing and maintaining mature bone at the bone–device interface is critical to the long-term success of prosthesis. Poor cell adhesion to orthopaedic and dental implants results in implant failure. Considerable effort has been devoted to alter the surface characteristics of these biomaterials in order to improve the initial interlocking of the device and skeleton. We investigated the effect of surface chemistry modification of titanium alloy (Ti–6Al–4V) with zinc, magnesium or alkoxide-derived hydroxy carbonate apatite (CHAP) on the regulation of key intracellular signalling proteins in human bone-derived cells (HBDC) cultured on these modified Ti–6Al–4V surfaces. Western blotting demonstrated that modifying Ti–6Al–4V with CHAP or Mg results in modulation of key intracellular signalling proteins. We showed an enhanced activation of Shc, a common point of integration between integrins and the Ras/Mapkinase pathway. Mapkinase pathway was also upregulated, suggesting its role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the Mg and CHAP modified Ti–6Al–4V. Thus surface modification with CHAP or Mg may contribute to successful osteoblast function and differentiation at the skeletal tissue–device interface. 相似文献
26.
Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kuismanen SA Moisio AL Schweizer P Truninger K Salovaara R Arola J Butzow R Jiricny J Nyström-Lahti M Peltomäki P 《The American journal of pathology》2002,160(6):1953-1958
The colorectum and uterine endometrium are the two most commonly affected organs in hereditary nonpolyposis colon cancer (HNPCC), but the genetic basis of organ selection is poorly understood. As tumorigenesis in HNPCC is driven by deficient DNA mismatch repair (MMR), we compared its typical consequence, instability at microsatellite sequences, in colorectal and endometrial cancers from patients with identical predisposing mutations in the MMR genes MLH1 or MSH2. Analysis of non-coding (BAT25, BAT26, and BAT40) and coding mononucleotide repeats (MSH6, MSH3, MLH3, BAX, IGF2R, TGF beta RII, and PTEN), as well as MLH1- and MSH2-linked dinucleotide repeats (D3S1611 and CA7) revealed significant differences, both quantitative and qualitative, between the two tumor types. Whereas colorectal cancers displayed a predominant pattern consisting of instability at the BAT loci (in 89% of tumors), TGF beta RII (73%), dinucleotide repeats (70%), MSH3 (43%), and BAX (30%), no such single pattern was discernible in endometrial cancers. Instead, the pattern was more heterogeneous and involved a lower proportion of unstable markers per tumor (mean 0.27 for endometrial cancers versus 0.45 for colorectal cancers, P < 0.001) and shorter allelic shifts for BAT markers (average 5.1 bp for unstable endometrial cancers versus 9.3 bp for colorectal cancers, P < 0.001). Among the individual putative "target" loci, PTEN instability was associated with endometrial cancers and TGF beta RII instability with colon cancers. The different instability profiles in endometrial and colorectal cancers despite identical genetic predisposition underlines organ-specific differences that may be important determinants of the HNPCC tumor spectrum. 相似文献
27.
Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion via toll-like receptor 2 signaling 总被引:2,自引:0,他引:2
Sturm A Rilling K Baumgart DC Gargas K Abou-Ghazalé T Raupach B Eckert J Schumann RR Enders C Sonnenborn U Wiedenmann B Dignass AU 《Infection and immunity》2005,73(3):1452-1465
Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be efficacious for the treatment of inflammatory bowel diseases, the underlying mechanisms of action still remain elusive. The aim of the present study was to analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3-stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA content, and caspase 3 expression were measured by flow cytometry to assess cell cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis modulators were determined by immunoblotting, and cytokine profiles were determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E. coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling. E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein expression, contributing to the reduction of T-cell proliferation. E. coli Nissle 1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor necrosis factor alpha, and gamma interferon but increased IL-10 production in PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2 dependent. The differential reaction of circulating and tissue-bound T cells towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle 1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the expansion of newly recruited T cells into the mucosa and limit intestinal inflammation, while already activated tissue-bound T cells may eliminate deleterious antigens in order to maintain immunological homeostasis. 相似文献
28.
Frank Wiedemann Ralf Link Konrad Pumpe Ulrich Jacobshagen Hans E. Schaefer Karl-Heinz Wiesmüller Rolf-Peter Hummel Günther Jung Wolfgang Bessler Traudel Bltz 《The Journal of pathology》1991,164(3):265-271
The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage. 相似文献
29.
Vrolijk JM Kaul A Hansen BE Lohmann V Haagmans BL Schalm SW Bartenschlager R 《Journal of virological methods》2003,110(2):201-209
Overall treatment results of chronic hepatitis C have improved markedly with the introduction of pegylated interferon-alpha (PEG–IFN-) and ribavirin combination therapy. However, cure rates in the most common genotype 1 infection are still unsatisfactory. IFN- dose–response studies on viral kinetics suggest that inadequate dosing might be a key factor but drug levels have hardly been tested, which is in part due to difficulties in measuring this cytokine in patient samples. We have shown recently that hepatitis C virus (HCV) replicons are highly sensitive to IFN-. In this report we tested whether the replicon system could be used as a sensitive bioassay to determine the amount of biologically active IFN- in serum or heparinized plasma of patients under therapy. To facilitate the measurements, a stably replicating subgenomic HCV RNA was developed that carries the gene encoding the firefly luciferase. Dose response studies with IFN- demonstrate that the amount of expressed luciferase directly correlates with the level of HCV replication. By using this cell-based assay, serum samples of HCV patients treated with different types and doses of IFN- were analyzed in parallel to IFN- standards made by serial dilutions of the same type of IFN- the patient was treated with. Based on nonlinear logistic models serum concentrations corresponding to 1.3–19 U/ml were determined in patients under standard or high dose IFN- therapy, and from 3.8 to 4.1 ng/ml in patients treated with PEG IFN-. In conclusion, the HCV-replicon based bioassay allows determining the levels of biologically active IFN- in serum and heparinized plasma of patients under treatment. 相似文献
30.
Generation, annotation, evolutionary analysis, and database integration of 20,000 unique sea urchin EST clusters 总被引:2,自引:0,他引:2
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)
Poustka AJ Groth D Hennig S Thamm S Cameron A Beck A Reinhardt R Herwig R Panopoulou G Lehrach H 《Genome research》2003,13(12):2736-2746
Together with the hemichordates, sea urchins represent basal groups of nonchordate invertebrate deuterostomes that occupy a key position in bilaterian evolution. Because sea urchin embryos are also amenable to functional studies, the sea urchin system has emerged as one of the leading models for the analysis of the function of genomic regulatory networks that control development. We have analyzed a total of 107,283 cDNA clones of libraries that span the development of the sea urchin Strongylocentrotus purpuratus. Normalization by oligonucleotide fingerprinting, EST sequencing and sequence clustering resulted in an EST catalog comprised of 20,000 unique genes or gene fragments. Around 7000 of the unique EST consensus sequences were associated with molecular and developmental functions. Phylogenetic comparison of the identified genes to the genome of the urochordate Ciona intestinalis indicate that at least one quarter of the genes thought to be chordate specific were already present at the base of deuterostome evolution. Comparison of the number of gene copies in sea urchins to those in chordates and vertebrates indicates that the sea urchin genome has not undergone extensive gene or complete genome duplications. The established unique gene set represents an essential tool for the annotation and assembly of the forthcoming sea urchin genome sequence. All cDNA clones and filters of all analyzed libraries are available from the resource center of the German genome project at http://www.rzpd.de. 相似文献