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排序方式: 共有1080条查询结果,搜索用时 15 毫秒
31.
Lo SM Choi M Liu J Jain D Boot RG Kallemeijn WW Aerts JM Pashankar F Kupfer GM Mane S Lifton RP Mistry PK 《Blood》2012,119(20):4731-4740
Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside. However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype. In the present study, the genetic basis of GD/T-cell acute lymphoblastic lymphoma in 2 affected siblings was deciphered through genomic analysis. GBA gene sequencing revealed homozygosity for a novel mutation, D137N. Whole-exome capture and massively parallel sequencing combined with homozygosity mapping identified a homozygous novel mutation in the MSH6 gene that leads to constitutional mismatch repair deficiency syndrome and increased cancer risk. Enzyme studies demonstrated that the D137N mutation in GBA is a pathogenic mutation, and immunohistochemistry confirmed the absence of the MSH6 protein. Therefore, precise phenotype annotation followed by individual genome analysis has the potential to identify genetic modifiers of GD, facilitate personalized management, and provide novel insights into disease pathophysiology. 相似文献
32.
D. H. Vasant A. Payton S. Mistry D. G. Thompson S. Hamdy 《Neurogastroenterology and motility》2013,25(2):162-e85
Background Recent evidence implicates brain‐derived neurotrophic factor (BDNF) in visceral hypersensitivity and pain in functional gastrointestinal disorders. We hypothesized that presence of the val66met polymorphism in the BDNF gene would be linked to increased esophageal sensitivity to electrical stimulation. Methods A total of 39 healthy volunteers (20 males, mean age 30) compliant with inclusion criteria after screening procedures were genotyped for BDNF polymorphisms and completed an Hospital Anxiety and Depression Scale (HADS) questionnaire. Sensory (ST) and pain (PT) thresholds in the proximal (PE) and distal (DE) esophagus were determined using electrical stimuli to a swallowed intraluminal catheter with bipolar electrodes by an investigator blinded to the subjects’ genotype. For comparison, somatic ST and PT (hand and foot) were also tested. HADS scores together with esophageal and somatic thresholds were then correlated with BDNF polymorphism status. Key Results Eleven of 39 (28%) volunteers had at least one Met allele (Met carriers). When compared with Val/Val, Met carriers had lower esophageal PT (Median PT [mA]: Val/Val vs Met carriers, PE; 49.4 vs 44.3, P = 0.033, DE: 63.8 vs 55.4, P = 0.045) with higher proportion of Val/Val subjects in the upper quartile for PT in both PE (P = 0.021) and DE (P = 0.033), yet similar somatic PT (Median PT [mA] Hand; 33.6 vs 38.0, P = 0.22, Foot; 44.7 vs 44.0, P = 0.48). Sensitivity results were independent of anxiety (P = 0.66) and depression (P = 0.33) scores. Conclusions & Inferences val66met BDNF polymorphisms are associated with increased esophageal sensitivity to experimental electrical stimulation. Thus, BDNF genotype may be a useful biomarker for electrical sensitivity in the healthy human esophagus. 相似文献
33.
Aude-Marine Paepegaey Matthew L. Barker David W. Bartlett Miten Mistry Nicola X. West Nicola Hellin Louise J. Brown Philip G. Bellamy 《Dental materials》2013
Objectives
To compare three instruments for their ability to quantify enamel loss after acid erosion.Methods
6 randomized parallel groups of bovine enamel samples were subjected to citric acid (higher acidity) or orange juice (lower acidity) erosion and remineralisation in a cycling model. Two protected shoulders were created on each of the samples using tape, to serve as reference for analysis. The time of exposure to each acid was varied, along with presence or absence of agitation. After treatment, samples were measured on 3 instruments capable of measuring step height: a contact profilometer (CP); a non-contact profilometer (NCP); and a confocal laser scanning microscope (CLSM) by three different examiners. Additionally, 3D (volume) step height was also measured using the CLSM.Results
Increasing acid concentration and exposure time resulted in greater erosion, as did agitation of samples while in acid solution. All instruments/methods identified the same statistically significant (p < 0.05) pair-wise differences between the treatments groups. Further, all four methods exhibited strong agreement (Intra-class correlation ≥ 0.96) in erosion level and were highly correlated, with correlations of 0.99 or higher in all cases.Significance
All instruments/methods used in this study produced very similar conclusions with regard to ranking of enamel loss, with data showing very high agreement between instruments. All instruments were found to be equally suited to the measurement of enamel erosion. 相似文献34.
Multi Drug Resistant Tuberculosis Beijing strains exhibit different drug-resistance mutations (DRM) in different locations. By comparing DRM in Beijing reported from Tuberculosis endemic and epidemic locations, we propose that DRM selected in a population cannot tolerate biologically available drugs in different populations resulting in further evolution through novel DRM. 相似文献
35.
Targeting stathmin in prostate cancer 总被引:4,自引:0,他引:4
Stathmin is the founding member of a family of microtubule-destabilizing proteins that regulate the dynamics of microtubule polymerization and depolymerization. Stathmin is expressed at high levels in a variety of human cancers and provides an attractive molecule to target in cancer therapies that disrupt the mitotic apparatus. We developed replication-deficient bicistronic adenoviral vectors that coexpress green fluorescent protein and ribozymes that target stathmin mRNA. The therapeutic potential of these recombinant adenoviruses was tested in an experimental androgen-independent LNCaP prostate cancer model. Adenovirus-mediated transfer of anti-stathmin ribozymes resulted in efficient transduction and marked inhibition of stathmin expression in these cells. Cells that were transduced with the anti-stathmin adenoviruses showed a dramatic dose-dependent growth inhibition. This was associated with accumulation of LNCaP cells in the G2-M phases of the cell cycle. A similar dose-dependent inhibition of clonogenic potential was also observed in cells infected with anti-stathmin adenoviruses. Morphologic and biochemical analysis of infected cells showed a marked increase in apoptosis characterized by detachment of the cells, increased chromatin condensation, activation of caspase-3, and fragmentation of internucleosomal DNA. If these findings are confirmed in vivo, it may provide an effective approach for the treatment of prostate cancer. 相似文献
36.
37.
Dhruti Mistry 《Drug and chemical toxicology》2018,41(2):162-168
It is both interesting and necessary to identify and develop nontoxic radioprotective compounds. Bleomycin (BLM), a known radiomimetic drug was used as a clastogen in the present study. The possible protective effects against BLM (15?μg/ml) induced clastogenicity by aqueous and methanolic extracts from Alstonia scholaris bark, stem and leaves were compared. The treatment of bark extracts significantly (p?0.01) reduced total chromosomal aberrations. Such a reduction was not seen in case of stem and leaf treatments. The dose of 50?μg/ml was fixed for all extracts throughout the study. To understand the mechanism involved with the protective property of bark extracts, sensitive G2 assay was performed. Lymphocyte cultures from 12 healthy volunteers were exposed to aqueous (50?μg/ml) and methanolic (50?μg/ml) extracts of A. scholaris bark alone as well as in combination with Bleomycin under two different growth phases, G0 and G2. There was a statistically significant reduction (p?0.05) in the total chromatid breaks in all cultures which were exposed at G2 phase as compared to respective cultures exposed at G0 phase. The highest level (p?0.0001) of reduction in total chromatid breaks was observed in cultures treated with aqueous bark extracts at G2 phase than those at G0 phase. This indicated that there could be certain compound(s) present in aqueous bark extracts which enhance DNA repair capacity. Therefore, the bark of A. scholaris could be further utilized to identify and bring out front line radio protective agents in the market with effective formulations. 相似文献
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40.
Amisha K. Mistry Chirag D. Nagda Dhruti C. Nagda Bharat C. Dixit Ritu B. Dixit 《Scientia pharmaceutica》2014,82(2):441-448
Natural gums are economical, easily available, and useful as tablet binders. In the present investigation, an attempt was made to formulate Ofloxacin tablets using three natural binders, namely Acacia arabica, Hibiscus esculentus, and xanthan gum. Such six batches of Ofloxacin tablets were prepared by using different types and amounts of the natural binders by the wet granulation method. The tablets were analyzed for their hardness, friability, and weight variation, and in vitro release was performed in a phosphate buffer at pH 6.8. The prepared tablets were also evaluated for their various release kinetics and similarity factors f2. The physical properties of the tablets containing the natural binders showed sufficient hardness, desirable disintegration time, and low friability. Their better percentage of drug release was observed as compared to the marketed formulation showing more than 85% drug release within 45 minutes. The in vitro release data was well-fitted into zero-order and the values of release exponent ‘n’ were between 0.303 and 0.514. The high similarity factor f2 of 64.50 was achieved with the best batch in comparison to the marketed tablets. The results obtained indicated that the gum Acacia arabica performed as well as gelatin compared to the other binders for the Ofloxacin tablet formulation. 相似文献