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101.
Numerical comparisons of two formulations of the logistic regressive models with the mixed model in segregation analysis of discrete traits. 总被引:4,自引:0,他引:4
Segregation analysis of discrete traits can be conducted by the classical mixed model and the recently introduced regressive models. The mixed model assumes an underlying liability to the disease, to which a major gene, a multifactorial component, and random environment contribute independently. Affected persons have a liability exceeding a threshold. The regressive logistic models assume that the logarithm of the odds of being affected is a linear function of major genotype effects, the phenotypes of older relatives, and other covariates. A formulation of the regressive models, based on an underlying liability model, has been recently proposed. The regression coefficients on antecedents are expressed in terms of the relevant familial correlations and a one-to-one correspondence with the parameters of the mixed model can thus be established. Computer simulations are conducted to evaluate the fit of the two formulations of the regressive models to the mixed model on nuclear families. The two forms of the class D regressive model provide a good fit to a generated mixed model, in terms of both hypothesis testing and parameter estimation. The simpler class A regressive model, which assumes that the outcomes of children depend solely on the outcomes of parents, is not robust against a sib-sib correlation exceeding that specified by the model, emphasizing testing class A against class D. The studies reported here show that if the true state of nature is that described by the mixed model, then a regressive model will do just as well. Moreover, the regressive models, allowing for more patterns of family dependence, provide a flexible framework to understand gene-environment interactions in complex diseases. 相似文献
102.
Detection of linkage under heterogeneity: comparison of the two-locus vs. admixture models. 总被引:9,自引:0,他引:9
L R Goldin 《Genetic epidemiology》1992,9(1):61-66
Linkage analysis under the two-locus model and the admixture model was compared on pedigree data for a common disease stimulated under a model of genetic heterogeneity. The ascertainment of families was designed so that the samples had a large proportion of families segregating for both disease loci. The two-locus linkage analysis model did not demonstrate increased power of detecting linkage or more accurate estimates of the recombination fraction, theta than did the admixture model linkage analysis. When a sample was purposely chosen so that all of the families were segregating for both loci, then the two-locus lod score analysis was better. However, the increased power depended on assuming the correct gene frequency for the linked locus. It can be concluded that under the conditions of genetic heterogeneity examined here, testing for linkage under the admixture model is the preferred method of analysis. However, this is not a general conclusion that can apply to all two-locus disease models. 相似文献
103.
Sandrine Cappellesso Jean-Fran?ois Valentin Bruno Giraudeau Marie-Denise Boulanger Azmi Al-Najjar Mathias Büchler Jean-Michel Halimi Hubert Nivet Pierre Bardos Yvon Lebranchu Hervé Watier 《Nephrology, dialysis, transplantation》2004,19(2):439-443
BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes. 相似文献
104.
105.
While the season-of-birth effect is one of the most consistent epidemiological features of schizophrenia, there is a lack
of consistency with respect to the interaction between season of birth and family history of schizophrenia. Apart from family
history, measures related to consanguinity can be used as proxy markers of genomic heterogeneity. Thus, these measures may
provide an alternate, indirect index of genetic susceptibility. We had the opportunity to explore the interaction between
season of birth and measure of consanguinity in well-described genetic isolates in Daghestan, some of which are known for
their relatively high prevalence of schizophrenia. Our previous population-genetic study showed Daghestan has an extremely
high genetic diversity between the ethnic populations and a low genetic diversity within them. The isolates selected for this
study include some with more than 200 and some with less than 100 generations of demographical history since their founding.
Based on pedigrees of multiply-affected families, we found that among individuals with schizophrenia, the measure of consanguinity
was significantly higher in the parents of those born in winter/spring compared to those born in summer/autumn. Furthermore,
compared to summer/autumn born, winter/spring born individuals with schizophrenia had an earlier age-of-onset, and more prominent
auditory hallucinations. Our results suggest that the offspring of consanguineous marriages, and thus those with reduced allelic
heterogeneity, may be more susceptible to the environmental factor(s) underpinning the season-of-the effect in schizophrenia. 相似文献
106.
107.
胃癌高系家族成员胃蛋白酶原C基因多态性及其诊断意义的探讨 总被引:1,自引:0,他引:1
采用限制性酶切片段长度多态性分析法,检测在胃癌高发区庄河检出的19例胃癌高系家族成员胃蛋白酶原C基因多态性,发现三种常见片段及一种稀有片段。对其中4例携带稀有片段的受检者进行了胃镜追踪观察,2.5年后发现1例早期胃癌。本文对此作了初步探讨。 相似文献
108.
SNP及其在畜牧业中的应用前景 总被引:4,自引:0,他引:4
张利平 《国外畜牧学(草食家畜)》2003,(3):30-32
SNP(single nucleotide polymorphisns-单核苷酸多态性)是继限制性片段长度多态性和微卫星之后,新发展起来的第3代分子标记。已成为一类新的遗传标记,广泛应用于基因定位、克隆和遗传多样性研究。本文介绍了SNP的特性、检测方法及其在畜牧业研究生产中的广泛利用前景。并提出了SNP研究中遇到的一些问题。 相似文献
109.
L. Cheng †‡ T. Enomoto§ T. Hirota† M. Shimizu † N. Takahashi† M. Akahoshi† A. Matsuda† Y. Dake§ S. Doi¶ K. Enomoto A. Yamasaki S. Fukuda X.-Q. Mao J. M. Hopkin M. Tamari† T. Shirakawa † 《Clinical and experimental allergy》2004,34(8):1192-1201
BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification. 相似文献
110.
T. Iwanaga †‡ A. McEuen† A. F. Walls† J. B. Clough† T. P. Keith§ S. Rorke† S. J. Barton† S. T. Holgate† J. W. Holloway † 《Clinical and experimental allergy》2004,34(7):1037-1042
BACKGROUND: Mast cell chymase has the potential to be an important mediator of inflammation and remodelling in the asthmatic lung. Previous studies have examined association between promoter polymorphism of the chymase gene (CMA1) and allergic phenotypes but the significance of this polymorphism is unclear. We have examined association of a CMA1 variant in relation to asthma in a large UK Caucasian family cohort. METHODS: A polymorphism of the CMA1 gene promoter (-1903G/A) was genotyped in 341 asthmatic families and in 184 non-asthmatic adults recruited from the UK PCR-RFLP based genotyping. Association with asthma diagnosis, atopy, specific and total IgE, and atopy and asthma severity was examined. RESULTS: Case-control studies did not reveal a significant difference in allele frequency between asthmatics and controls. A significant association was found between CMA1 genotypes and total IgE levels in subjects with self-reported eczema that remained significant after correction for multiple testing (median total serum IgE GG 297 kU/L, GA 144 kU/L, AA 48.4 kU/L, Pc=0.0032). CONCLUSION: These data suggest that CMA1 promoter polymorphism does not contribute to asthma susceptibility or severity but may be involved in regulating IgE levels in patients with eczema. 相似文献