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81.
The essential route to blood parasitaemia in malaria, erythrocyte invasion is facilitated by activation of the G-protein coupled receptor signaling pathway mediated by the β2-adrenoreceptor as one of the proteins on the surface of red blood cells. The effectiveness of bronchodilators and inhaled corticosteroids in the clinical treatment for asthma patients also depend on polymorphisms in the β2-adrenoreceptor gene (ADRB2). In a case control study, individuals affected by Plasmodium falciparum malaria, asthma and controls were tested for association of six ADRB2 single nucleotide polymorphisms (SNPs) viz. rs1042711, rs1801704, rs1042713, rs1042714, rs1042717 and rs1042718, by direct DNA sequencing. The rs1801704 locus was significantly associated with malaria when compared against controls. The rs1042713 polymorphism was associated with forced expiratory flow between 25% and 75% of the FVC in asthma patients, pre (p = 0.048) and post (p = 0.038) treatment measurements. Predicted haplotype of the six SNPs computed from genotype data showed T-T-A-C-G-C conferred significant risk of malaria (p = 0.02) whereas T-T-A-C-G-A was associated with risk of asthma (p = 0.02). The haplotype T-T-G-C-G-C was protective against both malaria (p = 0.02) as well as asthma (p = 0.026) and C-C-G-G-G-C was protective uniquely for asthma (p = 0.04). A significant outcome was that all variant alleles at the SNP loci were part of the haplotype conferring resistance to malaria disease and asthma, except rs1042713 and rs1042718 which showed very high frequency in asthma. The pairwise linkage disequilibrium (LD) estimates showed a distinct LD block of all SNP loci (D′ = 1 or >0.8) in malaria patients. This characteristic haplotype block was disrupted in the controls due to non-significant pairwise LD of the SNP loci; and a more extensive disruption of the block was noted in asthma patients. The study provides evidence for the proposed role of β2-adrenoreceptor mediated molecular mechanisms in etiology of malaria, as well as asthma disease and drug response, for further clinical and therapeutic application studies. 相似文献
82.
A variety of factors affect the development of endometriosis, including hormonal status and genetic factors. The growth of
endometriosis is stimulated by local estrogen production in conjunction with circulating estrogen. The CYP19 gene encodes
a steroid aromatase that catalyses the conversion of C-19 androgens to estrogens. This study investigated whether polymorphisms
of the CYP19 gene are associated with the risk of advanced endometriosis in Korean women. Blood samples were collected from
224 female patients with endometriosis of stages III and IV, as diagnosed by both pathologic and laparoscopic findings, and
from a control group comprising of 188 women undergoing laparoscopic surgery or laparotomy for nonmalignant lesions. Single-nucleotide
polymorphisms, restriction fragment length polymorphisms, and tetranucleotide tandem repeat polymorphisms were discriminated
by the polymerase chain reaction (PCR). Haplotype analysis was also performed. CYP19 115T>C, 240G>A, and 1531C>T polymorphisms
and [TTTA]n tetranucleotide repeat polymorphisms in the CYP19 gene and their haplotypes were not significantly associated with the risk
of endometriosis. The risk of endometriosis also did not increase significantly with the number of higher risk alleles of
the CYP19 gene. In conclusion, our findings suggest that CYP19 genetic polymorphisms are not associated with advanced-stage
endometriosis in Korean women. 相似文献
83.
Bouchlaka C Maktouf C Mahjoub B Ayadi A Sfar MT Sioud M Gueddich N Belhadjali Z Rebaï A Abdelhak S Dellagi K 《Journal of human genetics》2007,52(3):262-270
Megaloblastic anaemia 1 (MGA1) is a rare autosomal recessive condition characterized by selective intestinal vitamin B12 malabsorption
and proteinuria. More than 200 MGA1 patients have been identified worldwide, but the disease is relatively prevalent in Finland,
Norway and several Eastern Mediterranean regions. MGA1 is genetically heterogeneous and can be caused by mutations in either
the cubilin (CUBN) or the amnionless (AMN) gene. In the present study we investigated the molecular defect underlying MGA1 in nine Tunisian patients belonging to six
unrelated consanguineous families. Haplotype and linkage analyses, using microsatellite markers surrounding both CUBN and AMN genes, indicated that four out of the six families were likely to be linked to the CUBN gene. Patients from these families were screened for the Finnish, Mediterranean and Arabian mutations already published.
None of the screened mutations could be detected in our population. One family showed a linkage to AMN gene. Direct screening of the AMN gene allowed the identification of the c.208-2A>G mutation, previously described in a Jewish Israeli patient of Tunisian
origin and in Turkish patients. This suggests that the c.208-2A>G mutation may derive from a single Mediterranean founder
ancestor. For the last family, haplotype analysis excluded both CUBN and AMN genes, suggesting the existence of a third locus that may cause MGA1. 相似文献
84.
Amino T Ishikawa K Toru S Ishiguro T Sato N Tsunemi T Murata M Kobayashi K Inazawa J Toda T Mizusawa H 《Journal of human genetics》2007,52(8):643-649
The 16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA; Online Mendelian Inheritance in Man [OMIN] #117210) is
one of the most common ADCAs in Japan. Previously, we had reported that the patients share a common haplotype by founder effect
and that a C-to-T substitution (−16C>T) in the puratrophin-1 gene was strongly associated with the disease. However, recently, an exceptional patient without the substitution was reported,
indicating that a true pathogenic mutation might be present elsewhere. In this study, we clarified the disease locus more
definitely by the haplotype analysis of families showing pure cerebellar ataxia. In addition to microsatellite markers, the
single nucleotide polymorphisms (SNPs) that we identified on the disease chromosome were examined to confirm the borders of
the disease locus. The analysis of 64 families with the −16C>T substitution in the puratrophin-1 gene revealed one family showing an ancestral recombination event between SNP04 and SNP05 on the disease chromosome. The
analysis of 22 families without identifiable genetic mutations revealed another family carrying the common haplotype centromeric
to the puratrophin-1 gene, but lacking the −16C>T substitution in this gene. We concluded that the disease locus of 16q-ADCA was definitely
confined to a 900-kb genomic region between the SNP04 and the −16C>T substitution in the puratrophin-1 gene in 16q22.1. 相似文献
85.
86.
Durocher F Labrie Y Ouellette G;INHERIT BRCAs Simard J 《Journal of human genetics》2007,52(12):963-977
The poly(ADP-ribose) polymerase (PARP/ADPRT) protein family catalyzes the synthesis of cellular poly(ADP-ribose) following
DNA damage and is involved in genomic integrity by regulating cellular responses to DNA damage and apoptosis. Moreover, ADPRT
inhibition contributes to a protective effect against cancer development. These findings render ADPRT an attractive candidate susceptibility gene for breast cancer, and thus the goal of this study was to evaluate the possible
involvement of ADPRT sequence variations in breast cancer susceptibility. The complete sequence of the 23 exons and flanking intronic sequences
of the ADPRT gene was analyzed in 54 affected individuals from distinct high-risk non-BRCA1/2 French Canadian families. No deleterious truncating mutation was identified in the coding region. However, 34 sequence variations
were identified, among which seven are coding variants and seven are novel changes. All coding variants and intronic changes
located in the vicinity of the coding variants identified in the case series were also analyzed in a cohort of 73 unrelated
healthy French Canadian individuals. Interestingly, one missense variant (Pro377Ser) was observed in three different breast
cancer cases but was not present among unaffected individuals. We have conducted here an exhaustive detailed mutation and
haplotype tagging analysis of the ADPRT gene with regard to breast cancer, providing useful data for other large-scale association studies. Additional studies in
other cohorts and other populations are however needed to further evaluate the implication of the Pro377Ser missense variant
with regard to breast cancer susceptibility.
Other members of INHERIT BRCAs involved in clinical aspects of the study are listed in the Appendix.
J. Simard holds a Canada Research Chair in Oncogenetics. 相似文献
87.
Akin C Soto D Brittain E Chhabra A Schwartz LB Caughey GH Metcalfe DD 《Clinical immunology (Orlando, Fla.)》2007,123(3):268-271
Serum mast cell tryptase levels are used as a diagnostic criterion and surrogate marker of disease severity in mastocytosis. Approximately 29% of the healthy population lacks alpha tryptase genes; however, it is not known whether lack of alpha tryptase genes leads to variability in tryptase levels or impacts on disease severity in mastocytosis. We have thus analyzed tryptase haplotype in patients with mastocytosis, computing correlations between haplotype and plasma total and mature tryptase levels; and disease category. We found: (1) the distribution of tryptase haplotype in patients with mastocytosis appeared consistent with Hardy-Weinberg equilibrium and the distribution in the general population; (2) the disease severity and plasma tryptase levels were not affected by the number of alpha or beta tryptase alleles in this study; and (3) information about the tryptase haplotype did not provide any prognostic value about the severity of disease. Total and mature tryptase levels positively correlated with disease severity, as well as prothrombin time and partial thromboplastin time, and negatively correlated with the hemoglobin concentration. 相似文献
88.
Robitaille J Houde A Lemieux S Pérusse L Gaudet D Vohl MC 《Journal of molecular medicine (Berlin, Germany)》2007,85(2):129-137
Obesity is under the influence of genetic and nutritional factors. The objective was to verify whether variants in the gene encoding the carnitine palmitoyltransferase I (CPT1), a key enzyme in beta-oxidation of fatty acids, are associated with obesity phenotypes, alone or in interaction with fat intake. Sequencing of CPT1 was performed in 40 overweight subjects and 4 controls. Genotypes were determined in 351 French-Canadians. Fat intake was evaluated by a food frequency questionnaire. We identified 14 genetic variations in CPT1A and 26 in CPT1B. Nine variants within CPT1B and one variant within CPT1A were selected for further analyses based on the minor allele frequency (>10%) or on potential functional impact. A significant association between obesity phenotypes (BMI, weight, and waist girth) and CPT1B c.282-18C > T and p.E531K variants was observed (p < 0.05) No other association was found with variants in CPT1A and CPT1B. When subjects were divided into six groups according to p.E531K genotypes and further on the basis of fat using the median value as a cutoff point (34.4% of energy), BMI, weight, and waist girth were higher in E531/K531 on a high-fat diet compared to E531/K531 subjects under a low-fat diet (p = 0.004, p = 0.006, p = 0.003, respectively). There was no difference among E531/E531 and K531/K531. Similar results were obtained with the CPT1A p.A275T variant as BMI and waist girth were higher in A275/A275 on a high fat compared to A275/A275 subjects on a low-fat diet. Among carriers of the T275 allele, obesity indices were not affected by fat intake (p = 0.05 and p = 0.008 for BMI and waist girth, respectively). Among variants within the CPT1B gene, 13 haplotypes were inferred and the two most frequent haplotypes, H7 (38.0%) and H5 (27.7%), were kept for diplotype analysis. These haplotypes were not associated with indices of obesity, but as observed with the CPT1B E531K variant fat intake modulated this association. In conclusion, this finding suggests that indices of obesity might be modulated by an interaction between CPT1 variants and fat intake. 相似文献
89.
Asgeir Lande Irene Andersen Torstein Egeland Benedicte A. Lie Marte K. Viken 《Human immunology》2018,79(7):527-529
We report HLA-A, -C, -B, -DRB1, -DQB1 and -DPB1 allele frequencies and estimated haplotype frequencies from 4514 healthy Norwegians who volunteered to participate in the Norwegian Bone Marrow Donor Registry. HLA genotyping was conducted on a Next Generation Sequencing platform. Data were analyzed using Arlequin and Pypop software. No significant deviations from Hardy-Weinberg Equilibrium were noted at any of the loci studied. We discuss the representability for the Norwegian population and argue that the presented HLA data could serve as a Norwegian reference panel. 相似文献
90.
Yvonne R. Thorstenson Lisa E. Creary Huang Huang Virginie Rozot Tracy T. Nguyen Farbod Babrzadeh Sandeep Kancharla Marilyn Fukushima Raquel Kuehn Chunlin Wang Ming Li Sujatha Krishnakumar Michael Mindrinos Marcelo A. Fernandez Viña Thomas J. Scriba Mark M. Davis 《Human immunology》2018,79(12):839-847
The development of next-generation sequencing (NGS) methods for HLA genotyping has already had an impact on the scope and precision of HLA research. In this study, allelic resolution HLA typing was obtained for 402 individuals from Cape Town, South Africa. The data were produced by high-throughput NGS sequencing as part of a study of T-cell responses to Mycobacterium tuberculosis in collaboration with the University of Cape Town and Stanford University. All samples were genotyped for 11 HLA loci, namely HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, -DRB3, -DRB4, and -DRB5. NGS HLA typing of samples from Cape Town inhabitants revealed a unique cohort, including unusual haplotypes, and 22 novel alleles not previously reported in the IPD-IMGT/HLA Database. Eight novel alleles were in Class I loci and 14 were in Class II. There were 62 different alleles of HLA-A, 72 of HLA-B, and 47 of HLA-C. Alleles A123:17, A143:01, A129:11, A168:27:01, A101:23, B114:01:01, B115:10:01, B139:10:01, B145:07, B182:02:01 and C108:04:01 were notably more frequent in Cape Town compared to other populations reported in the literature. Class II loci had 21 different alleles of DPA1, 46 of DPB1, 27 of DQA1, 26 of DQB1, 41 of DRB1, 5 of DRB3, 4 of DRB4 and 6 of DRB5. The Cape Town cohort exhibited high degrees of HLA diversity and relatively high heterozygosity at most loci. Genetic distances between Cape Town and five other sub-Saharan African populations were also calculated and compared to European Americans. 相似文献