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21.
Massimo Pignatelli Tareq W. Ansari Pat Gunter Dan Liu Shinji Hirano Masatoshi Takeichi Günter Klppel Nicholas R. Lemoine 《The Journal of pathology》1994,174(4):243-248
Epithelial cadherin (E-cadherin) is a Ca2+-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumours. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumours (grade I) (4/14, 28 per cent) (P=0·012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P=0·043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer. 相似文献
22.
Evidence of a diverse T cell receptor repertoire for acetylcholine receptor,the autoantigen of myasthenia gravis 总被引:1,自引:0,他引:1
Infante AJ Baillargeon J Kraig E Lott L Jackson C Hämmerling GJ Raju R David C 《Journal of autoimmunity》2003,21(2):167-174
We utilized two methods to look for T cell clonal expansions in myasthenia gravis (MG). We analyzed TCRBV CDR3 length polymorphism (spectratyping) to look for evidence of clonal expansion of CD4 or CD8 T cells directly from peripheral blood of MG patients. No statistically significant differences were found between the diversity of TCR repertoires in MG patients compared to normal control individuals when analyzed as groups. Rare oligoclonal expansions were detected in some individual MG patients but the significance of these findings is unclear. Next, we analyzed a panel of T cell hybridomas from acetylcholine receptor (AChR) immunized, MG-susceptible HLA-DR3 transgenic mice. The epitope specificity, TCRBV gene usage and CDR3 sequences of these hybridomas were highly diverse. We conclude there is only limited evidence for restricted TCR repertoire usage in human MG and suggest this may be due to the inability of HLA-DR molecules to select for restricted TCR recognition of AChR epitopes. 相似文献
23.
Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter 总被引:12,自引:0,他引:12
Heinz A Braus DF Smolka MN Wrase J Puls I Hermann D Klein S Grüsser SM Flor H Schumann G Mann K Büchel C 《Nature neuroscience》2005,8(1):20-21
Major depression is conditionally linked to a polymorphism of the human serotonin transporter gene (SLC6A4). During the presentation of aversive, but not pleasant, pictures, healthy carriers of the SLC6A4 short (s) allele showed stronger activation of the amygdala on functional magnetic resonance imaging. s carriers also showed greater coupling between the amygdala and the ventromedial prefrontal cortex, which may contribute to the abnormally high activity in the amygdala and medial prefrontal cortex seen in major depression. 相似文献
24.
A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin 总被引:31,自引:1,他引:31 下载免费PDF全文
Schotta G Lachner M Sarma K Ebert A Sengupta R Reuter G Reinberg D Jenuwein T 《Genes & development》2004,18(11):1251-1262
Histone lysine methylation is a central modification to mark functionally distinct chromatin regions. In particular, H3-K9 trimethylation has emerged as a hallmark of pericentric heterochromatin in mammals. Here we show that H4-K20 trimethylation is also focally enriched at pericentric heterochromatin. Intriguingly, H3-K9 trimethylation by the Suv39h HMTases is required for the induction of H4-K20 trimethylation, although the H4 Lys 20 position is not an intrinsic substrate for these enzymes. By using a candidate approach, we identified Suv4-20h1 and Suv4-20h2 as two novel SET domain HMTases that localize to pericentric heterochromatin and specifically act as nucleosomal H4-K20 trimethylating enzymes. Interaction of the Suv4-20h enzymes with HP1 isoforms suggests a sequential mechanism to establish H3-K9 and H4-K20 trimethylation at pericentric heterochromatin. Heterochromatic H4-K20 trimethylation is evolutionarily conserved, and in Drosophila, the Suv4-20 homolog is a novel PEV modifier to regulate position-effect variegation. Together, our data indicate a function for H4-K20 trimethylation in gene silencing and further suggest H3-K9 and H4-K20 trimethylation as important components of a repressive pathway that can index pericentric heterochromatin. 相似文献
25.
Detection of DNA damage after hyperbaric oxygen (HBO) therapy 总被引:4,自引:0,他引:4
Hyperbaric oxygen HBO therapy is successfully used for the treatmentof a variety of conditions. However, exposure to high concentrationsof oxygen is known to induce damage to cells, possibly due toan increased oxygen radical production. As reactive oxygen speciesalso cause DNA damage, we investigated the DNA-damaging effectof HBO with the alkaline version of the single cell gel testcomet assay. Oxidative DNA base modifications were determinedby converting oxidized DNA bases to strand breaks using bacterialformamidopyrimidine-DNA glycosylase FPG, a DNA repair enzyme,which specifically nicks DNA at sites of 8-oxo-guanines andformamidopyrimidines. HBO treatment under therapeutic conditionsclearly and reproducibly induced DNA damage in leukocytes ofall test subjects investigated. Increased DNA damage was foundimmediately at the end of the treatment, while 24 h later, noeffect was found. Using FPG protein we detected significantoxidative base damage after HBO treatment DNA damage was detectedonly after the first treatment and not after further treatmentsunder the same conditions, indicating an increase in antioxidantdefences. DNA damage did not occur when the HBO treatment wasstarted with a reduced treatment time which was then increasedstepwise.
3To whom correspondence should be addressed 相似文献
26.
Emerging electronic health record models present numerous challenges to health care systems, physicians, and regulators. This article provides explanation of some of the reasons driving the development of the electronic health record, describes two national electronic health record models (currently developing in the United States and Australia) and one distributed, personal model. The US and Australian models are contrasted in their different architectures ("pull" versus "push") and their different approaches to patient autonomy, privacy, and confidentiality. The article also discusses some of the professional, practical, and legal challenges that health care providers potentially face both during and after electronic health record implementation. 相似文献
27.
Joachim Böttcher M.D. Alexander Pfeil Anders Rosholm Ph.D. Max-Ludwig Schäfer Ansgar Malich M.D. Alexander Petrovitch M.D. Bettina Seidl Gabriele Lehmann M.D. Hans-Joachim Mentzel M.D. Gert Hein M.D. Gunter Wolf M.D. Werner A. Kaiser M.D. M.S. 《Journal of digital imaging》2006,19(3):279-288
Purpose Our study evaluates digital x-ray radiogrammetry (DXR) and Radiogrammetry Kit (RK) as a new diagnostic method for the measurement
of disease-related osteoporosis including quantification of joint space narrowing dependent on the severity of rheumatoid
arthritis (RA).
Materials and Methods A total of 172 unselected patients with RA underwent computerized measurements of bone mineral density (BMD) and metacarpal
index (MCI) by DXR, as well as a semiautomated measurement of joint space distances at the metacarpal–phalangeal articulation
(JSD-MCP 2–5), both were analyzed from plain radiographs of the nondominant hand.
Results Correlations between DXR-BMD and DXR-MCI vs. parameters of RK were all significant (0.34 < R < 0.61; p < 0.01). An expected negative association was observed between RK parameters and the different scoring methods (−0.27 < R < −0.59). The maximum relative decrease in BMD vs. MCI as measured by DXR between the highest and lowest RA severity group
was −27.7% vs. −27.5% (p < 0.01) for the modified Larsen Score, whereas the minimal value of relative DXR-BMD and DXR-MCI reduction could be documented
for the Sharp Erosion Score (−20.8% vs. −26.8%; p < 0.01). The relative reduction of mean JSD-MCP using RK significantly varied from −25.0% (Sharp Erosion Score) to −41.2%
(modified Larsen Score). In addition, an excellent reproducibility of DXR and RK could be verified.
Conclusion DXR in combination with RK could be a promising, widely available diagnostic tool to supplement the different scoring methods
of RA with quantitative data, allowing an earlier and improved diagnosis and more precision in determining disease progression. 相似文献
28.
29.
Unsöld B Kerst G Brousos H Hübner M Schreiber R Nitschke R Greger R Bleich M 《Pflügers Archiv : European journal of physiology》2000,441(2-3):368-378
Previous studies have shown that heteromultimeric KCNQ1/KCNE1 (KvLQT1/minK) channels and homomultimeric KCNQ1 (KvLQT1) channels exhibit different current properties, e.g. distinct kinetics and different sensitivities to drugs. In this study we report on the divergent responses to internal pH changes and further characterize some of the current properties of the human isoforms of KCNQ1 and KCNE1 expressed in Chinese hamster ovary (CHO) cells or Xenopus laevis oocytes. Decreasing the bath temperature from 37 degrees C to 20 degrees C increased the half-activation time by a factor of 5 for KCNQ1/KCNE1 currents (IKs) but by only twofold (not significant) for KCNQ1 currents (IK) in CHO cells. Acidification of cytosolic pH (pHi) increased IKs but decreased 1K whereas intracellular alkalinization decreased I(Ks) but increased IK. pHi-induced changes in intracellular Ca2+ activity ([Ca2+]i) did not correlate with the current responses. At 20 degrees C mefenamic acid (0.1 mM) significantly augmented IKs but slightly decreased IK. It changed the slow activation kinetics of I(Ks) to an instantaneous onset. The form of the current/voltage (I/V) curve changed from sigmoidal to almost linear. In contrast, at 37 degrees C, mefenamic acid also increased I(Ks) but slowed the activation kinetics and shifted the voltage activation to more hyperpolarized values without markedly affecting the sigmoidal shape of the I/V curve. The potassium channel blockers clotrimazole and tetrapentylammonium (TPeA) inhibited I(Ks) with a lower potency than I(K). These results show that coexpression of KCNE1 reversed pH regulation of KCNQ1 from inhibition to activation by acidic pHi. In addition, KCNE1 altered the pharmacological properties and sensitivity to temperature of KCNQ1. The pH-dependence of I(Ks) might be of clinical and pathophysiological relevance in the pathogenesis of ischaemic cardiac arrhythmias. 相似文献
30.
The formation of IncM plasmid encoded pili is dependent on the incubation temperature of the corresponding host strains. By labelling the short, rigid M pili with the donor specific bacteriophage luminal diameter M, the presence of pili at 30 degrees C but not at 37 degrees C incubation temperature could be demonstrated for E. coli K12 substrains carrying different IncM group plasmids. In contrast, such a temperature dependence of M pilus formation is not observed in S. typhimurium substrains. 相似文献