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81.
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry 总被引:8,自引:1,他引:8
Nistico L; Buzzetti R; Pritchard LE; Van der Auwera B; Giovannini C; Bosi E; Larrad MT; Rios MS; Chow CC; Cockram CS; Jacobs K; Mijovic C; Bain SC; Barnett AH; Vandewalle CL; Schuit F; Gorus FK; Tosi R; Pozzilli P; Todd JA 《Human molecular genetics》1996,5(7):1075-1080
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus
is determined by a combination of environmental and genetic factors, which
include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin
gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2
cannot explain the clustering of type 1 diabetes in families, and a role
for other genes is inferred. In the present report we describe linkage and
association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte
associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong
candidate gene for T cell- mediated autoimmune disease because it encodes a
T cell receptor that mediates T cell apoptosis and is a vital negative
regulator of T cell activation. In addition, we provide supporting evidence
that CTLA-4 is associated with susceptibility to Graves' disease, another
organ- specific autoimmune disease.
相似文献
82.
Regina Raz Kam Cheung Leona Ling David E. Levy 《Somatic Cell and Molecular Genetics》1995,21(2):139-145
The species specificity of interferons (IFNs) depends on restricted recognition of these ligands by multisubunit cell surface receptors. Expression of the human receptor subunit IFNAR in mouse cells conferred sensitivity only to one subtype of human IFN, IFN-B. Other genes on human chromosome 21 were required for responses to other subtypes of type I IFN. In contrast, IFNAR expression in hamster cells did not confer sensitivity to any human IFN tested, including IFN-B. Using human-hamster somatic cell hybrids, we mapped theIfnabr gene, encoding a ligand-binding subunit of the IFN-/ (type I) receptor, to human chromosome 21.Ifnabr colocalized withIfnar to the distal region of q22.1. The presence of a chromosomal fragment encoding IFNABR and IFNAR was also not sufficient to confer sensitivity to human IFN. In contrast, hybrids carrying in addition the region 21q22.2 showed a full response to human IFN-B, suggesting that a gene located in this region encodes a third factor required for type I IFN receptor activity. 相似文献
83.
84.
Wong WW Doyle TC Cheung P Olson TM Reisler E 《Journal of muscle research and cell motility》2001,22(8):665-674
The molecular mechanisms by which different mutations in actin lead to distinct cardiomyopathies are unknown. Here, actin
mutants corresponding to α-cardiac actin mutations causing hypertrophic cardiomyopathy [(HCM) P164A and A331P] and dilated
cardiomyopathy [(DCM) R312H and E361G] were expressed in yeast and purified for in vitro functional studies. While P164A appeared unaltered compared to wild-type (WT) actin, A331P function was impaired. A331P showed
reduced stability in circular dichroism melting experiments; its monomer unfolding transition was 10°C lower compared to WT
actin. Additionally, in vitro filament formation was hampered, and yeast cell cultures were temperature sensitive, implying perturbations in actin–actin
interactions. Filament instability of the A331P mutant actin could lead to actomyosin dysfunction observed in HCM. Yeast strains
harboring the R312H mutation did not grow well in culture, suggesting that cell viability is compromised. The E361G substitution
is located at an α-actinin binding region where the actin filament is anchored. The mutant actin, though unaltered in the
in vitro motility and standard actomyosin functions, had a threefold reduction in α-actinin binding. This could result in impairment
of force-transduction in muscle fibers, and a DCM phenotype.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
85.
Evaluation of quantitative PCR and branched-chain DNA assay for detection of hepatitis B virus DNA in sera from hepatocellular carcinoma and liver transplant patients 总被引:4,自引:0,他引:4
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This study evaluated the applicability of quantitative PCR (Q-PCR) and branched-chain DNA assays for detection of hepatitis B virus (HBV) DNA in sera. For 42 samples, the detection rates were 81 and 41%, respectively, with a correlation coefficient of 0.633. The Q-PCR is useful for early monitoring of HBV load in high-risk patients. 相似文献
86.
Tang NL Hui J Law LK Lam YY Chan KY Yeung WL Chan AY Cheung KL Fok TF 《Human mutation》2000,16(5):446
Glutaric acidemia type I is caused by mutations of the glutaryl-CoA dehydrogenase (GCDH) gene resulting in loss of GCDH enzyme activity. Patients present with progressive dystonia and lesions in basal ganglia. Dietary treatment, when instituted from the early neonatal period, markedly reduces dystonia and morbidity. Early diagnosis and prenatal diagnosis will be facilitated by knowledge of locally prevalent GCDH mutations. Several common GCDH mutations have been found in different ethnic groups. GCDH mutations were studied in 5 Chinese glutaric acidemia type I families. We detected two novel recurrent mutations (A219T and IVS10-2A>C) which were found in two unrelated families. An asymptomatic carrier of IVS10-2A>C was also found on screening of 120 individuals. Other mutations were identified, including two other novel (R386G & IVS3+1G>A) and two known mutations (G178R & R355H). Fibroblasts from patients carrying the novel mutations were confirmed to be deficient for GCDH activity. This is the first report of GCDH mutations describing recurrent mutations in Chinese patients. The carrier rate of IVS10-2A>C may be particularly high in Chinese. 相似文献
87.
Chloe Miu Mak Ching-Wan Lam Sidney Tam Ching-Lung Lai Lik-Yuen Chan Sheung-Tat Fan Yu-Lung Lau Sik-To Lai Patrick Yuen Joannie Hui Chun-Cheung Fu Ka-Sing Wong Wing-Lai Mak Kong Tze Sui-Fan Tong Abby Lau Nancy Leung Aric Hui Ka-Ming Cheung Chun-Hung Ko Yiu-Ki Chan Oliver Ma Tai-Nin Chau Alexander Chiu Yan-Wo Chan 《Journal of human genetics》2008,53(4):375-375
88.
89.
Detection and deletion of motion artifacts in electrogastrogram using feature analysis and neural networks 总被引:6,自引:0,他引:6
Electrogastrogram is a surface measurement of gastric myoelectrical activity, and electrogastrography has been an attractive
method for physiological and pathophysiological studies of the stomach due to its nonivasive nature. Motion artifacts, however,
ruin the electrogastrogram (EGG), and make the analysis very difficult and sometimes even impossible. They must be eliminated
from EGG signals before analysis. Up to now, this can only be done by visual inspection, which is not only time-consuming
but also subjective. In this study, a method using feature analysis and neural networks has been developed to realize automatic
detection and elimination of the motion artifacts in EGG recordings by computer. Experiments were conducted to investigate
the characteristics of different motion artifacts. Useful features were extracted, and different combinations of the features
used as the input of the neural network were compared to obtain the optimal performance for the detection of motion artifacts
using the artificial neural network. 相似文献
90.
The role of IL-10 in the regulation of ocular autoimmune disease was
studied in experimental autoimmune uveoretinitis (EAU) elicited in mice by
immunization with the retinal antigen interphotoreceptor retinoid binding
protein. IL-10-deficient mice were susceptible to EAU, indicating that
pathogenesis can occur without presence of IL-10. Treatment of normal mice
with IL-10 for 5 days after uveitogenic immunization ameliorated subsequent
EAU scores, and down-regulated antigen-specific production of tumor
necrosis factor-alpha and IFN- gamma. A concomitant treatment with IL-4
further reduced disease, and resulted in emergence of antigen-specific IL-4
and IL-10 production, as well as in enhancement of the IgG1 antibody
isotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, was
able to inhibit the function of differentiated uveitogenic T cells in
culture. Expression of mRNA for Th1 and Th2 cytokines in the eye during the
course of EAU showed that while a Th1 pattern predominated early, IL-10
mRNA expression coincided with down-regulation of the Th1 response and
resolution of EAU. Systemic neutralization of IL-10 during the expression
phase of EAU resulted in elevated disease scores. Our results suggest that
endogenous IL-10 limits expression of EAU and may play a role in the
natural resolution of disease. The data further suggest that exogenous
IL-10 may be useful in therapeutic control of autoimmune uveitis. While
IL-10 by itself is sufficient to suppress Th1 effector development and
function, a concomitant administration of IL-4 is required to shift the
autoimmune response towards a non-pathogenic Th2 pathway.
相似文献