全文获取类型
收费全文 | 19219篇 |
免费 | 1566篇 |
国内免费 | 71篇 |
专业分类
耳鼻咽喉 | 163篇 |
儿科学 | 627篇 |
妇产科学 | 530篇 |
基础医学 | 2904篇 |
口腔科学 | 284篇 |
临床医学 | 2220篇 |
内科学 | 3823篇 |
皮肤病学 | 592篇 |
神经病学 | 1927篇 |
特种医学 | 489篇 |
外科学 | 1852篇 |
综合类 | 156篇 |
一般理论 | 20篇 |
预防医学 | 2167篇 |
眼科学 | 344篇 |
药学 | 1163篇 |
中国医学 | 36篇 |
肿瘤学 | 1559篇 |
出版年
2024年 | 32篇 |
2023年 | 247篇 |
2022年 | 428篇 |
2021年 | 965篇 |
2020年 | 586篇 |
2019年 | 765篇 |
2018年 | 825篇 |
2017年 | 625篇 |
2016年 | 705篇 |
2015年 | 719篇 |
2014年 | 879篇 |
2013年 | 1143篇 |
2012年 | 1652篇 |
2011年 | 1684篇 |
2010年 | 851篇 |
2009年 | 743篇 |
2008年 | 1150篇 |
2007年 | 1169篇 |
2006年 | 997篇 |
2005年 | 969篇 |
2004年 | 880篇 |
2003年 | 788篇 |
2002年 | 679篇 |
2001年 | 106篇 |
2000年 | 81篇 |
1999年 | 102篇 |
1998年 | 128篇 |
1997年 | 110篇 |
1996年 | 76篇 |
1995年 | 80篇 |
1994年 | 65篇 |
1993年 | 48篇 |
1992年 | 46篇 |
1991年 | 51篇 |
1990年 | 48篇 |
1989年 | 26篇 |
1988年 | 24篇 |
1987年 | 29篇 |
1986年 | 20篇 |
1985年 | 31篇 |
1984年 | 30篇 |
1983年 | 26篇 |
1982年 | 20篇 |
1981年 | 32篇 |
1980年 | 21篇 |
1978年 | 24篇 |
1977年 | 11篇 |
1976年 | 12篇 |
1973年 | 11篇 |
1971年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
81.
Knopik VS Sparrow EP Madden PA Bucholz KK Hudziak JJ Reich W Slutske WS Grant JD McLaughlin TL Todorov A Todd RD Heath AC 《Psychological medicine》2005,35(5):625-635
BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect. 相似文献
82.
83.
SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression
下载免费PDF全文
![点击此处可从《Genes & development》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nuclear matrix attachment regions (MARs) are regulatory DNA sequences that are important for higher-order chromatin organization, long-range enhancer function, and extension of chromatin modifications. Here we characterize a novel cell type-specific MAR-binding protein, SATB2, which binds to the MARs of the endogenous immunoglobulin micro locus in pre-B cells and enhances gene expression. We found that SATB2 differs from the closely related thymocyte-specific protein SATB1 by modifications of two lysines with the small ubiquitive related modifier (SUMO), which are augmented specifically by the SUMO E3 ligase PIAS1. Mutations of the SUMO conjugation sites of SATB2 enhance its activation potential and association with endogenous MARs in vivo, whereas N-terminal fusions with SUMO1 or SUMO3 decrease SATB2-mediated gene activation. Sumoylation is also involved in targeting SATB2 to the nuclear periphery, raising the possibility that this reversible modification of a MAR-binding protein may contribute to the modulation of subnuclear DNA localization. 相似文献
84.
Miguel A Alejandre-Alcázar Petar D Shalamanov Oana V Amarie Julia Sevilla-Pérez Werner Seeger Oliver Eickelberg Rory E Morty 《Developmental dynamics》2007,236(10):2825-2835
Bone morphogenetic proteins (BMPs) play important roles in early lung development. No study to date has addressed a role for BMP signaling in late lung development. We describe changes in the expression and localization of BMP receptors (Bmpr1a, Bmpr1b, and Bmpr2) and Smad (Smad1, Smad4, Smad5, and Smad8) intracellular signaling proteins during the saccular and alveolarization stages of late lung development. BMP signaling, assessed by Smad1/5 phosphorylation, nuclear translocation, and induction of id1, id2, and id3 gene expression, was evident throughout late lung development. Our data indicate that BMP signaling is active during late lung development, and points to roles for the BMP system in septal and vascular development, and in the homeostasis of the epithelial layer of large conducting airways in the mature lung. 相似文献
85.
Monoclonal Antibodies to Trypanosoma cruzi Inhibit Motility and Nucleic Acid Synthesis of Culture Forms 总被引:2,自引:1,他引:2
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Maria Julia Manso Alves Masamichi Aikawa Ruth S. Nussenzweig 《Infection and immunity》1983,39(1):377-382
Monoclonal antibodies were raised against the surface of epimastigotes and metacylic trypomastigotes of Trypanosoma cruzi, as shown by electron microscopy, agglutination, and immunofluorescence. The antibodies were stage specific but not strain specific. A deleterious effect of the antibodies on T. cruzi culture forms was shown by the drastic reduction of parasite motility and incorporation of nucleic acid precursors. Some fraction of the parasite population, however, was viable and replicated and infected mouse macrophages in culture. The antibodies were found to also mediate complement-induced lysis of culture forms of T. cruzi. 相似文献
86.
87.
Cell extract-derived differentiation of embryonic stem cells 总被引:1,自引:0,他引:1
Various means have been used to encourage the differentiation of embryonic stem cells (ESCs) toward specific lineages, including growth factor administration, genetic modification, and coculture with relevant cells/tissues. Cell extract-based reprogramming has recently been used to derive mature cells from nonrelated phenotypes. In this communication, we tested whether this in vitro reprogramming approach can be used to direct ESC differentiation. Permeabilized murine ESCs exposed to extracts of murine type II pneumocytes showed increased expression of surfactant protein C and its corresponding mRNA, reflecting enhanced differentiation of pneumocytes. Subsequent differentiation to a type I phenotype was demonstrated by expression of aquaporin 5. Pneumocyte formation occurred quicker than with growth factor-induced differentiation. Our findings establish that ESCs can be differentiated in vitro using cellular extracts. This model provides a tool for analysis of the key factors involved in the differentiation of ESCs to type II pneumocytes. 相似文献
88.
Meisel C Gerloff T Kirchheiner J Mrozikiewicz PM Niewinski P Brockmöller J Roots I 《Journal of molecular medicine (Berlin, Germany)》2003,81(3):154-167
Adverse drug reactions and ineffective drug treatment are responsible for a large health care burden. Considerable variability in drug response makes the prediction of the individual reaction difficult. Pharmacogenetics can help to individualize drug treatment in accordance with the genetic make-up of the patient. Drug response is best understood as a complex interplay between pharmacokinetics, pharmacodynamics, and other disease-associated factors. There are a large number of genetic variants in the enzymes of phase I and phase II drug metabolism, in drug transporters, and drug targets, all of which account for differences in drug response. The polymorphisms in the cytochrome P450 enzyme system have been investigated most extensively. Genotype-based dose adjustment which should ensure "bioequivalent" drug concentrations in all patients has been derived from pharmacokinetic parameters, but this approach will have to be verified in prospective studies. Drug transport has recently been recognized as a further crucial determinant in pharmacokinetics. The effect of genetics on disease susceptibility and drug treatment has been studied quite extensively; however, hardly any of this progress is at present reflected in routine health care. The integration of pharmacogenetic factors in clinical trials requires novel considerations for study design and data interpretation. It is to be hoped that the new science bioinformatics will (a) help us identify the contribution of genetics to disease and treatment response and will (b) create data-processing devices which help the physician in the face of the enormously expanding scientific knowledge in selecting the best individually adapted treatment for the patient. 相似文献
89.
90.
Giuliana Properzi Sandro Franca Villa Gianfranco Poccia Paolo Aloisi Xu-Hong Gu Giorgio Terenghi Julia M. Polak 《The Journal of pathology》1993,169(2):269-277
Diabetic neuropathy affects both sensory and autonomic peripheral nerve fibres. Vasoactive intestinal polypeptide (VIP) is present in autonomic fibres which modulate sweat secretion, while calcitonin gene-related peptide (CGRP) is localized to cutaneous sensory fibres. In this study, immunohistochemistry and image analysis were used to assess changes of VIP and CGRP, and of the pan-neuronal marker protein gene-product (PGP)-9.5, in skin biopsies of 18 patients affected by type 1 diabetes (age range 18–46 years) and from seven aged-matched controls. Patients were divided into three groups: group 1 (n=6), with diabetes for 6 months to 3 years; group 2 (n=5), with the disease for 5–10 years; and group 3 (n=7), with diabetes for more than 10 years. VIP immunoreactivity (IR) and PGP-9.5-IR were significantly reduced around sweat glands (P <0.005) in groups 2 and 3. Epidermal CGRP-IR and PGP-9.5-IR were significantly reduced in group 3 (P <0.05). Twenty-eight per cent (5/18) of all patients showed high VIP-IR around sweat glands (>95 per cent confidence limits of controls) and all of these patients had diabetes for less than 3 years. Conversely, 55 per cent (10/18) of patients had low VIP-IR (<5 per cent confidence limit of controls). The latter, compared with the former, showed a significantly longer duration of diabetes (Fisher exact test P=0·002), presence of clinical autonomic neuropathy (Fisher exact test P=0.04), and a reduced sural nerve conduction velocity (Fisher exact test P=0.04). These results suggest that quantitative immunohistochemical analysis of peptide-containing cutaneous nerves allows an objective evaluation of nerve fibre alterations at early stages of diabetes than is currently possible with neurophysiological functional tests. 相似文献