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51.
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Danielle te Vruchte Aruna Jeans Frances M. Platt Daniel John Sillence 《Journal of inherited metabolic disease》2010,33(3):261-270
Glycosphingolipid storage diseases are a group of inherited metabolic diseases in which glycosphingolipids accumulate due to their impaired lysosomal breakdown. Splenic B cells isolated from NPC1, Sandhoff, GM1-gangliosidosis and Fabry disease mouse models showed large (20- to 30-fold) increases in disease specific glycosphingolipids and up to a 4-fold increase in cholesterol. The magnitude of glycosphingolipid storage was in the order NPC1 > Sandhoff ∼ GM1 gangliosidosis > Fabry. Except for Fabry disease, glycosphingolipid storage led to an increase in the lysosomal compartment and altered glycosphingolipid trafficking. In order to investigate the consequences of storage on B cell function, the levels of surface expression of B cell IgM receptor and its associated components were quantitated in Sandhoff B cells, since they are all raft-associated on activation. Both the B cell receptor, CD21 and CD19 had decreased cell surface expression. In contrast, CD40 and MHC II, surface receptors that do not associate with lipid rafts, were unchanged. Using a pulse chase biotinylation procedure, surface B cell receptors on a Sandhoff lymphoblast cell line were found to have a significantly decreased half-life. Increased co-localization of fluorescently conjugated cholera toxin and lysosomes was also observed in Sandhoff B cells. Glycosphingolipid storage leads to the enhanced formation of lysosomal lipid rafts, altered endocytic trafficking and increased degradation of the B cell receptor. 相似文献
53.
A. te Slaa D.E.J.G.J. Dolmans G.H. Ho P.G.H. Mulder J.C.H. van der Waal H.G.W. de Groot L. van der Laan 《European journal of vascular and endovascular surgery》2010,39(5):635-642
ObjectiveTo investigate the efficacy of A-V impulse technology (A-V) for oedema prevention and treatment following PTFE femoropopliteal surgery.DesignProspective randomized clinical trial.Materials36 patients undergoing PTFE femoropopliteal bypass reconstructions, either being treated postoperatively with a compression stocking (CS) (Group-1, n = 19) or with A-V (Group-2, n = 17).MethodsPatients in treatment group-1 used a CS postoperatively during 1 week day and night, patients in group-2 were treated with A-V postoperatively at night during one week. The lower leg circumference was measured preoperatively and at five postoperative time points.ResultsLimb circumference has increased postoperatively on day 1 (CS 1.5%/A-V 1.4%), on day 4 (5.7%/6.3%), on day 7 (6.6%/6.1%), on day 14 (7.9%/7.7%) and on day 90 (5.8%/5.2%). Differences between treatment groups were not significant. A re-operation gives a significant 3.9% increase in circumference as compared to a first operation (95% CI: 1.5–6.4%; p = 0.002).ConclusionNo significant differences were found in the extent of developed edema between the groups following PTFE femoropopliteal bypass surgery. A redo peripheral bypass operation results in significantly more postoperative oedema than a first-time performed bypass operation. 相似文献
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Contrasting roles of IL-12p40 and IL-12p35 in the development of hapten-induced colitis. 总被引:7,自引:0,他引:7
Luisa Camoglio Nicole P Juffermans Maikel Peppelenbosch Anje A te Velde Fibo J ten Kate Sander J H van Deventer Manfred Kopf 《European journal of immunology》2002,32(1):261-269
IL-12(p70), a heterodimer composed of two subunits (p35 and p40), is a key cytokine for Th1 mediated inflammatory responses. We dissected the role of IL-12 in the development of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis by studying mice deficient in IL-12p40, IL-12p35, or IL-12Rbeta1. TNBS-treated IL-12Rbeta1(-/-) and IL-12p35(-/-) mice developed only a mild disease associated with low level IL-18 expression in IL-12p35(-/-) mice. In contrast, IL-12p40(-/-) mice developed more severe colitis than wild-type mice associated with high level colonic IL-18 expression. Administration of IL-12p40 neutralizing mononuclear antibody dramatically increased pathology in IL-12p35(-/-) mice similar to disease scored in IL-12p40(-/-) mice. Numbers of IFN-gamma-producing cells infiltrating the lamina propria were comparably augmented in the different groups of IL-12-mutant and wild-type mice. These results demonstrate that IL-12p40, in contrast to IL-12p70, inhibits TNBS-induced colitis and IL-18 expression independent of IFN-gamma. 相似文献
56.
M. Hussein Gasem Helmia Farida Ahmed Ahmed Juli?te A. Severin Agus Suryanto Bambang Isbandrio Henri A. Verbrugh Rudy A. Hartskeerl Peterhans J. van den Broek 《Journal of clinical microbiology》2016,54(1):197-199
We report four Indonesian cases meeting the clinical and radiological criteria for community-acquired pneumonia and other findings suggestive of leptospirosis. Quantitative PCR (qPCR) analyses of serum and urine samples and serology confirmed the diagnosis of leptospirosis in each. Results of qPCR analysis of throat swabs were concordant with those obtained with acute-phase serum samples, which suggests its potential for use as a noninvasive diagnostic tool for leptospirosis. 相似文献
57.
Lowe CE Cooper JD Chapman JM Barratt BJ Twells RC Green EA Savage DA Guja C Ionescu-Tîrgovişte C Tuomilehto-Wolf E Tuomilehto J Todd JA Clayton DG 《Genes and immunity》2004,5(4):301-305
We have previously shown that the selection of haplotype tag single nucleotide polymorphisms (htSNPs) and their statistical analysis in a multi-locus transmission/disequilibrium test (TDT) results in a more cost-effective genotyping strategy in disease association studies of genes by minimising redundancy due to linkage disequilibrium between SNPs. Further savings can be achieved by the use of a two-stage genotyping strategy. This approach is illustrated here in conjunction with the multi-locus TDT in determining whether common alleles of the immune regulatory genes RANK and its ligand TRANCE (RANKL) are associated with type 1 diabetes (T1D). A saving of approximately 75% of potential genotyping reactions could be made with minimal loss of power. There was little evidence from our analysis for association between the TRANCE and RANK genes and T1D in the populations tested. 相似文献
58.
Kok K Dijkhuizen T Swart YE Zorgdrager H van der Vlies P Fehrmann R te Meerman GJ Gerssen-Schoorl KB van Essen T Sikkema-Raddatz B Buys CH 《European journal of medical genetics》2005,48(3):250-CGH
In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere. 相似文献
59.
Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130 总被引:6,自引:0,他引:6 下载免费PDF全文
Dannenberg JH Schuijff L Dekker M van der Valk M te Riele H 《Genes & development》2004,18(23):2952-2962
The retinoblastoma gene family consists of three genes: RB, p107, and p130. While loss of pRB causes retinoblastoma in humans and pituitary gland tumors in mice, tumorigenesis in other tissues may be suppressed by p107 and p130. To test this hypothesis, we have generated chimeric mice from embryonic stem cells carrying compound loss-of-function mutations in the Rb gene family. We found that Rb/p107- and Rb/p130-deficient mice were highly cancer prone. We conclude that in a variety of tissues tumor development by loss of pRB is suppressed by its homologs p107 and p130. The redundancy of the retinoblastoma proteins in vivo is reflected by the behavior of Rb-family-defective mouse embryonic fibroblasts in vitro. 相似文献
60.