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991.
Tereza Pavlová Filip Zlámal Zbyněk Šplíchal Josef Tomandl Zuzana Hodická Pavel Ventruba 《The journal of maternal-fetal & neonatal medicine》2018,31(14):1811-1818
Objectives: The aim of the study is to investigate differences in visfatin concentrations between mothers with term and preterm birth (PTB) and between mothers who delivered within seven days and after more than seven days following admission for PTB/preterm premature rupture of membranes (PPROMs).Methods: Maternal peripheral blood and cord blood were collected from 56 mothers with PTB (31 with PPROM) and 71 mothers with term delivery (three with PPROM).Results: Maternal visfatin concentration was significantly higher for given gestational age in PTBs compared to term deliveries (p?=?.021) and also in mothers who delivered within seven days after admission for PTB or PPROM, compared to those who delivered after more than seven days (p?=?.027; p?=?.039). Cord blood visfatin concentration was found to be decreased in preterm compared to term infants (p?=?.007).Conclusions: Visfatin in both maternal and fetal circulation may play an important role in the pathogenesis of PTB/PPROM and could be used to distinguish between women who will deliver in a short period of time after clinical presentation of PTB/PPROM and those who deliver later. Nevertheless, additional research is necessary in order to identify its direct involvement in PTB/PPROM. 相似文献
992.
Structure-Activity–Dependent Regulation of Cell Communication by Perfluorinated Fatty Acids using in Vivo and in Vitro Model Systems 下载免费PDF全文
Brad L. Upham Joon-Suk Park Pavel Babica Iva Sovadinova Alisa M. Rummel James E. Trosko Akihiko Hirose Ryuichi Hasegawa Jun Kanno Kimie Sai 《Environmental health perspectives》2009,117(4):545-551
Background
Perfluoroalkanoates, [e.g., perfluorooctanoate (PFOA)], are known peroxisome proliferators that induce hepatomegaly and hepatocarcinogenesis in rodents, and are classic non-genotoxic carcinogens that inhibit in vitro gap-junctional intercellular communication (GJIC). This inhibition of GJIC is known to be a function of perfluorinated carbon lengths ranging from 7 to 10.Objectives
The aim of this study was to determine if the inhibition of GJIC by PFOA but not perfluoropentanoate (PFPeA) observed in F344 rat liver cells in vitro also occurs in F344 rats in vivo and to determine mechanisms of PFOA dysregulation of GJIC using in vitro assay systems.Methods
We used an incision load/dye transfer technique to assess GJIC in livers of rats exposed to PFOA and PFPeA. We used in vitro assays with inhibitors of cell signaling enzymes and antioxidants known to regulate GJIC to identify which enzymes regulated PFOA-induced inhibition of GJIC.Results
PFOA inhibited GJIC and induced hepatomegaly in rat livers, whereas PFPeA had no effect on either end point. Serum biochemistry of liver enzymes indicated no cytotoxic response to these compounds. In vitro analysis of mitogen-activated protein kinase (MAPK) indicated that PFOA, but not PFPeA, can activate the extracellular receptor kinase (ERK). Inhibition of GJIC, in vitro, by PFOA depended on the activation of both ERK and phosphatidylcholine-specific phospholipase C (PC-PLC) in the dysregulation of GJIC in an oxidative-dependent mechanism.Conclusions
The in vitro analysis of GJIC, an epigenetic marker of tumor promoters, can also predict the in vivo activity of PFOA, which dysregulated GJIC via ERK and PC-PLC. 相似文献993.
Patterson TJ Ngo M Aronov PA Reznikova TV Green PG Rice RH 《Chemical research in toxicology》2003,16(12):1624-1631
Sodium arsenite is much more potent than sodium arsenate in producing adverse effects in animals and in cultured cells. Although arsenate may exhibit toxicity as a phosphate analogue, its potency in vivo appears to be enhanced by reduction to arsenite. To understand the relative importance of this reduction, which is critical in evaluating the responsiveness of cell culture models to the different oxidation states and thus to elucidating the mechanism of arsenic action, present work has correlated the extent of reduction with biological activity in human keratinocytes. The results show that at biologically relevant concentrations, arsenate reduction to appreciable levels required several days, helping rationalize a previous empirical observation that it was approximately one-third as potent as arsenite. The relatively low conversion rate also emphasizes a limitation of culture; arsenate was nearly as efficacious as arsenite, but the time required for it to reach maximal effect exceeded ordinary medium change intervals. In keratinocytes, an important role for purine nucleoside phosphorylase in the reduction could not be demonstrated, indicating that another pathway is dominant in this cell type. Methylation of inorganic arsenic, uptake of methylated forms, and their reduction were all very slow. These findings suggest that the reduced methylated forms have only a small contribution to skin carcinogenesis unless they are supplied through the circulation. In parallel experiments, trivalent antimony was similar to arsenite in potency and efficacy, whereas pentavalent antimony was virtually without biological effect. Conversion of antimony in the pentavalent to the trivalent oxidation state was not detectable in keratinocytes. These findings emphasize the importance of intracellular reduction of the metalloids for biological effects. 相似文献
994.
Paprocka J Kajor M Jamroz E Jezela-Stanek A Seeman P Marszał E 《Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences》2006,44(4):290-294
Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disease with sensory and motor nerve palsies usually precipitated by trivial trauma or compression. In the majority of cases HNPP is caused by deletion of the peripheral myelin protein 22 gene (PMP22) on chromosome 17p11.2. The authors present a family case with genetically proven HNPP. 相似文献
995.
996.
Stefanie Huhn Melanie Bevier Barbara Pardini Alessio Naccarati Ludmila Vodickova Jan Novotny Pavel Vodicka Kari Hemminki Asta Försti 《Cancer causes & control : CCC》2014,25(6):759-769
Purpose
The first two studies aiming for the high-throughput identification of the somatic mutation spectrum of colorectal cancer (CRC) tumors were published in 2006 and 2007. Using exome sequencing, they described 69 and 140 candidate cancer genes (CAN genes), respectively. We hypothesized that germline variants in these genes may influence CRC risk, similar to APC, which is causing CRC through germline and somatic mutations.Methods
After excluding the well-established CRC genes APC, KRAS, TP53, and ABCA1, we analyzed 35 potentially functional single-nucleotide polymorphisms (SNPs) in 10 CAN genes (OBSCN, MLL3, PKHD1, SYNE1, ERCC6, FBXW7, EPHB6/TRPV6, ELAC1/SMAD4, EPHA3, and ADAMTSL3) using KBiosciences Competitive Allele‐Specific PCR? genotyping assays. In addition to CRC risk (1,399 CRC cases, 838 controls), we also considered the influence of the SNPs on patients’ survival (406 cases).Results
In spite of the fact that our in silico analyses suggested functional relevance for the studied genes and SNPs, our data did not support a strong influence of the studied germline variants on CRC risk and survival. The strongest association with CRC risk and survival was found for MLL3 (rs6464211, OR 1.50, p = 0.002, dominant model; HR 2.12, p = 0.020, recessive model). Two SNPs in EPHB6/TRPV6 (dominant model) showed marginal associations with survival (rs4987622 HR 0.58 p = 0.028 and rs6947538 HR 0.64, p = 0.036, respectively).Conclusion
Although somatic mutations in the CAN genes have been related to the development and progression of various types of cancers in several next-generation sequencing or expression analyses, our study suggests that the studied potentially functional germline variants are not likely to affect CRC risk or survival. 相似文献997.
Landi D Gemignani F Naccarati A Pardini B Vodicka P Vodickova L Novotny J Försti A Hemminki K Canzian F Landi S 《Carcinogenesis》2008,29(3):579-584
Recent evidence indicate that small non-coding RNA molecules,called micro-RNAs (miRNAs), can bind to the 3' untranslatedregions (UTRs) of messenger RNAs and interfere with their translation,thereby regulating cell growth, differentiation, apoptosis andtumorigenesis. Genetic polymorphisms can reside on miRNA-bindingsites. Thus, it is conceivable that the miRNA regulation maybe affected by polymorphisms on the 3' UTRs. Since gene deregulationis one of the key mechanisms by which cells can progress tocancer, we hypothesize that common polymorphisms within miRNA-targetbinding sites could play a role in the individual risk of cancer.In the present study, we selected the 3' UTRs of 104 genes candidatefor colorectal cancer (CRC) and we identified putative miRNA-bindingsites by specialized algorithms (PicTar, DianaMicroT, miRBase,miRanda, TargetScan and microInspector). Fifty-seven single-nucleotidepolymorphisms (SNPs) were identified in miRNA-binding sites.We evaluated the SNPs for their ability to affect the bindingof the miRNA with its target, by assessing the variation ofGibbs free energy between the two alleles of each SNP. We foundeight common polymorphisms that were further investigated bya case–control association studies. The study was carriedout on a series of cases and controls from Czech Republic, apopulation with the highest worldwide incidence of CRC. We foundstatistically significant associations between risk of CRC andvariant alleles of CD86 [odds ratio (OR) = 2.74; 95% confidenceinterval (CI) = 1.24–6.04, for the variant homozygotes]and INSR genes (OR = 1.94; 95% CI = 1.03–3.66, for thevariant homozygotes). These results are the first reportingpositive association between miRNA-binding SNPs sequences andcancer risk. Abbreviations: CRC, colorectal cancer; CI, confidence interval; mRNA, messenger RNA; miRNA, micro-RNA; MAF, minor allele frequency; nt, nucleotide; OR, odds ratio; SNP, single-nucleotide polymorphism; UTR, untranslated region Received October 24, 2007; revised December 6, 2007; accepted December 22, 2007. 相似文献
998.
999.
1000.
Xuemei Yu Bruno Sainz Jr. Pavel A. Petukhov Susan L. Uprichard 《Antimicrobial agents and chemotherapy》2012,56(12):6109-6120
With 2 to 3% of the worldwide population chronically infected, hepatitis C virus (HCV) infection continues to be a major health care burden. Unfortunately, current interferon-based treatment options are not effective in all patients and are associated with significant side effects. Consequently, there is an ongoing need to identify and develop new anti-HCV therapies. Toward this goal, we previously developed a cell-based HCV infection assay for antiviral compound screening based on a low-multiplicity-of-infection approach that uniquely allows for the identification of antiviral compounds that target cell culture-derived HCV (HCVcc) at any step of the viral infection cycle. Using this assay, here we report the screening of the NCI Diversity Set II library, containing 1,974 synthesized chemical compounds, and the identification of compounds with specific anti-HCV activity. In combination with toxicity counterscreening, we identified 30 hits from the compound library, 13 of which showed reproducible and dose-dependent inhibition of HCV with mean therapeutic indices (50% cytotoxic concentration [CC50]/50% effective concentration [EC50]) of greater than 6. Using HCV pseudotype and replicon systems of multiple HCV genotypes, as well as infectious HCVcc-based assembly and secretion analysis, we determined that different compounds within this group of candidate inhibitors target different steps of viral infection. The compounds identified not only will serve as biological probes to study and further dissect the biology of viral infection but also should facilitate the development of new anti-HCV therapeutic treatments. 相似文献