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Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.   相似文献   
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This paper discusses the need to create specific programs for the training of researchers in epidemiology, a field that has traditionally been ignored by the graduate programs in public health. This is due, in part, to the emphasis that has been placed on the training of professionals in other areas of public health. The paper also includes the results of a consensus exercise developed during the curricular design of the Masters Program in Epidemiology of the School of Medicine of the National Autonomous University of Mexico. The technique used during the consensus exercise was the TKJ, which allows the presentation of ideas and possible solutions for a specific problem. This is probably the first published experience in the use of such a technique for the design of an academic curriculum. Taking as a base the general characteristics of the students, the substantive, disciplinary and methodological subjects were chosen. The results showed a need for a multidisciplinary approach based on modern methodologies of statistics and epidemiology. The usefulness of the results of the curricular design and the superiority of this method to reach consensus is also discussed.  相似文献   
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目的 :研究低发病的中国汉族人群维生素D受体基因 (VDRG)BsmⅠ 位点单核苷酸多态性 (SNP)与前列腺癌的关系 ,探讨不同种族前列腺癌发病的基因差异。 方法 :收集中国北方地区汉族人群 10 3例前列腺癌病人及10 6例健康对照者外周血标本 ,应用变性高效液相色谱 (DHPLC)检测VDRG第 8内含子BsmⅠ多态位点 ,并对该位点SNP分布进行分析。 结果 :BsmⅠ 多态位点bb、Bb、BB基因型和等位基因在北方地区汉族前列腺癌病人及对照者中的分布频率差异无显著性 (P >0 .0 5 ) ,基因型分布频率分别为 92 .2 3%、7.77%、0和 94.34 %、5 .6 6 %、0 ;等位基因B、b分别为 3.88%、96 .12 %和 2 .91%、97.0 9%,而与高发病人群的分布相比有显著不同。 结论 :VDRGBsmⅠ多态性在低发病的中国汉族人群与前列腺癌无相关 ,其分布与高发病人群有明显差异 ,提示VDRGBsmⅠ多态性可能是前列腺癌发病种族差异的原因之一。  相似文献   
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A study aimed at detecting risk factors for high blood lead levels in Mexico City inhabitants, undertaken at the local National Institute of Public Health, is described. Measurements of blood lead levels for a sample of 300 civil servants were related to several potential risk factors. The statistical analysis was based on analysis of variance and logistic regression. The results of the analysis seem to suggest differences in blood levels by sex, zone of residence, hours of transportation and eating habits, such as the consumption of canned meals and the use of "earthenware dishes" in the preparation of meals. The nature of the study is exploratory, but it seems to suggest directions of research in the complex problem of lead levels in people of polluted cities.  相似文献   
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While an unstable CTG triplet repeat expansion is responsible for myotonic dystrophy, the mechanism whereby this genetic defect induces the disease remains unknown. To detect proteins binding to CTG triplet repeats, we performed bandshift analysis using as probes double- stranded DNA fragments having CTG repeats [ds(CTG)6-10] and single- stranded oligonucleotides having CTG repeats ss(CTG)8 or RNA CUG triplet repeats (CUG)8. The source of protein was nuclear and cytoplasmic extracts of HeLa cells, fibroblasts and myotubes. Proteins binding to the double-stranded DNA repeat [ds(CTG)6-10], were inhibited by nonlabeled ds(CTG)6-10, but not by a non-specific DNA fragment (USF/AD-ML). Another protein binding to ssCTG probe and RNA CUG probe was inhibited by nonlabeled (CTG)8 and (CUG)8. Nonlabeled oligos with different triplet repeat sequences, ss(CAG)8 or ss(CGG)8, did not inhibit binding to the ss(CTG)8 probe. However, when labeled as probes, the (CAG)8 and (CGG)8 bound to proteins distinct from the CTG proteins and binding was inhibited by nonlabeled (CAG)8 or (CGG)8 respectively. The protein binding only to the RNA repeat (CUG)8 was inhibited by nonlabeled (CUG)8 but not by nonlabeled single- or double-stranded CTG repeats. Furthermore, the CUG-BP exhibited no binding to an RNA oligonucleotide of triplet repeats of the same length but having a different sequence, CGG. The CUG binding protein was localized to the cytoplasm, whereas dsDNA binding proteins were localized to the nuclear extract. Thus, several trinucleotide binding proteins exist and their specificity is determined by the triplet sequence. The novel protein, CUG-BP, is particularly interesting since it binds to triplet repeats known to be present in myotonin protein kinase mRNA which is responsible for myotonic dystrophy.   相似文献   
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We have previously observed the repeated presence of low but detectable amounts of the trophoblast marker pregnancy-specific beta1-glycoprotein (SP1) in the serum of some women undergoing in-vitro fertilization (IVF) treatment around the time of oocyte retrieval. The occurrence of these signals seemed to be restricted to a defined group of patients which also showed a lower pregnancy success rate in a preliminary study. To test our hypothesis we have analysed 173 consecutive cycles leading to an embryo transfer. Fifty-four cycles (31%) had a serum SP1 level of at least 0.1 ng/ml between days embryo transfer -5 and embryo transfer (group A). Five pregnancies were obtained in this group (pregnancy rate = 9.3%), while in group B, defined by the absence of detectable SP1 before embryo transfer (119 cycles), 36 ongoing pregnancies were achieved (30.3%). Ten of the 41 pregnancies were achieved in 33 first-time non-pregnant patients undergoing further attempts during the study period. Again the pregnancy rate was higher in the first-time group B women (9/23 versus 1/10 for group A). Patients tended to remain in their groups A or B, the latter being associated with a better immediate as well as subsequent chance for pregnancy. Group A cycles had a significantly lower endometrial thickness two days before oocyte retrieval than group B (P = 0.0011). We postulate that the presence of an unknown, maternal and progesterone- or follicle stimulating hormone-independent factor in some patients could stimulate tonic ectopic SP1 synthesis and at the same time negatively influence endometrial development.   相似文献   
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We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.   相似文献   
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