全文获取类型
收费全文 | 31683篇 |
免费 | 2783篇 |
国内免费 | 2217篇 |
专业分类
耳鼻咽喉 | 243篇 |
儿科学 | 365篇 |
妇产科学 | 419篇 |
基础医学 | 3820篇 |
口腔科学 | 518篇 |
临床医学 | 4259篇 |
内科学 | 4484篇 |
皮肤病学 | 280篇 |
神经病学 | 1673篇 |
特种医学 | 1056篇 |
外国民族医学 | 24篇 |
外科学 | 3322篇 |
综合类 | 5074篇 |
现状与发展 | 4篇 |
一般理论 | 2篇 |
预防医学 | 2328篇 |
眼科学 | 814篇 |
药学 | 3310篇 |
39篇 | |
中国医学 | 1615篇 |
肿瘤学 | 3034篇 |
出版年
2024年 | 127篇 |
2023年 | 540篇 |
2022年 | 1367篇 |
2021年 | 1665篇 |
2020年 | 1299篇 |
2019年 | 1078篇 |
2018年 | 1116篇 |
2017年 | 1004篇 |
2016年 | 982篇 |
2015年 | 1485篇 |
2014年 | 1807篇 |
2013年 | 1625篇 |
2012年 | 2262篇 |
2011年 | 2540篇 |
2010年 | 1571篇 |
2009年 | 1270篇 |
2008年 | 1685篇 |
2007年 | 1711篇 |
2006年 | 1552篇 |
2005年 | 1560篇 |
2004年 | 1009篇 |
2003年 | 1096篇 |
2002年 | 822篇 |
2001年 | 633篇 |
2000年 | 686篇 |
1999年 | 793篇 |
1998年 | 495篇 |
1997年 | 495篇 |
1996年 | 338篇 |
1995年 | 315篇 |
1994年 | 325篇 |
1993年 | 184篇 |
1992年 | 228篇 |
1991年 | 187篇 |
1990年 | 157篇 |
1989年 | 160篇 |
1988年 | 130篇 |
1987年 | 107篇 |
1986年 | 77篇 |
1985年 | 84篇 |
1984年 | 30篇 |
1983年 | 19篇 |
1982年 | 15篇 |
1981年 | 13篇 |
1980年 | 9篇 |
1979年 | 21篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1929年 | 1篇 |
1905年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
993.
994.
995.
XY Dai Y Cai DD Mao YF Qi C Tang Q Xu Y Zhu MJ Xu X Wang 《Journal of molecular and cellular cardiology》2012,53(4):509-520
Intermedin, a novel member of calcitonin gene-related peptide family, is an endogenous cardiovascular-protective peptide. Because intermedin exists in human atherosclerotic plaque, we studied the role of intermedin in macrophage scavenger receptor A (SR-A)-mediated foam-cell formation and atherogenesis. In an in vitro foam-cell formation model (induced by acetylated low-density lipoprotein [AcLDL]) with mouse (C57BL/6J) macrophages, intermedin reduced AcLDL uptake and binding, decreased intracellular cholesterol content, and suppressed both mRNA and protein levels of SR-A. Simultaneously, intermedin increased phosphatase and tensin homolog (PTEN) protein levels by increasing PTEN phosphorylation and inhibiting ubiquitin-mediated PTEN degradation. These effects were blocked by the intermedin receptor antagonist or cAMP-protein kinase A inhibitors. PTEN overexpression mimicked the inhibitory effects of intermedin on SR-A expression and AcLDL uptake. However, knockdown of PTEN by short-hairpin RNA completely blocked all inhibitory effects of intermedin. Furthermore, in apolipoprotein E-deficient (apoE(-/-)) mice, 6-week intermedin infusion reduced AcLDL uptake and SR-A mRNA and protein levels and increased PTEN protein level in peritoneal macrophages. PTEN level was increased and SR-A expression decreased in parallel in macrophages in atherosclerotic lesions. Thus, intermedin inhibited atherosclerosis in apoE(-/-) mice. Increased stability of PTEN by intermedin leads to SR-A inhibition in macrophages, which ameliorates foam-cell formation and atherosclerosis in apoE(-/-) mice. 相似文献
996.
Celestino-Soper PB Violante S Crawford EL Luo R Lionel AC Delaby E Cai G Sadikovic B Lee K Lo C Gao K Person RE Moss TJ German JR Huang N Shinawi M Treadwell-Deering D Szatmari P Roberts W Fernandez B Schroer RJ Stevenson RE Buxbaum JD Betancur C Scherer SW Sanders SJ Geschwind DH Sutcliffe JS Hurles ME Wanders RJ Shaw CA Leal SM Cook EH Goin-Kochel RP Vaz FM Beaudet AL 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(21):7974-7981
We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism. 相似文献
997.
You H Tsutsui S Hameed S Kannanayakal TJ Chen L Xia P Engbers JD Lipton SA Stys PK Zamponi GW 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(5):1737-1742
N-methyl-d-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrP(C)), a key copper-binding protein in the CNS. Acute ablation of PrP(C) by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrP(C) interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aβ(1-42) (10 nM-5 μM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aβ(1-42), copper chelators, or PrP(C) inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrP(C), one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aβ(1-42) might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrP(C)-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor. 相似文献
998.
Weijing Cai Maya Ramdas Li Zhu Xue Chen Gary E. Striker Helen Vlassara 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(39):15888-15893
The epidemics of insulin resistance (IR) and type 2 diabetes (T2D) affect the first world as well as less-developed countries, and now affect children as well. Persistently elevated oxidative stress and inflammation (OS/Infl) precede these polygenic conditions. A hallmark of contemporary lifestyle is a preference for thermally processed nutrients, replete with pro-OS/Infl advanced glycation endproducts (AGEs), which enhance appetite and cause overnutrition. We propose that chronic ingestion of oral AGEs promotes IR and T2D. The mechanism(s) involved in these findings were assessed in four generations of C57BL6 mice fed isocaloric diets with or without AGEs [synthetic methyl-glyoxal-derivatives (MG+)]. F3/MG+ mice manifested increased adiposity and premature IR, marked by severe deficiency of anti-AGE advanced glycation receptor 1 (AGER1) and of survival factor sirtuin 1 (SIRT1) in white adipose tissue (WAT), skeletal muscle, and liver. Impaired 2-deoxy-glucose uptake was associated with marked changes in insulin receptor (InsR), IRS-1, IRS-2, Akt activation, and a macrophage and adipocyte shift to a pro-OS/inflammatory (M1) phenotype. These features were absent in F3/MG− mice. MG stimulation of 3T3-L1 adipocytes led to suppressed AGER1 and SIRT1, and altered InsR, IRS-1, IRS-2 phosphorylation, and nuclear factor kappa-light chain enhancer of activated B cells (Nf-κB) p65 acetylation. Gene modulation revealed these effects to be coregulated by AGER1 and SIRT1. Thus, prolonged oral exposure to MG-AGEs can deplete host-defenses AGER1 and SIRT1, raise basal OS/Infl, and increase susceptibility to dysmetabolic IR. Because exposure to AGEs can be decreased, these insights provide an important framework for alleviating a major lifestyle-linked disease epidemic. 相似文献
999.
Jørgensen KK Lindström L Cvancarova M Castedal M Friman S Schrumpf E Foss A Isoniemi H Nordin A Holte K Rasmussen A Bergquist A Vatn MH Boberg KM 《Scandinavian journal of gastroenterology》2012,(47):1021-1029
Abstract Objective. Several studies have implicated primary sclerosing cholangitis (PSC) as an additional risk factor for colorectal neoplasia in inflammatory bowel disease (IBD). Some reports have indicated that the risk is even higher in PSC-IBD patients after liver transplantation (Ltx), but this issue is controversial. We aimed to compare the risk of colorectal neoplasia in PSC-IBD patients before and after Ltx and to identify risk factors for colorectal neoplasia post-transplant. Material and methods. In a multicenter study within the Nordic Liver Transplant Group, we assessed the risk of colorectal neoplasia by using the competing risk regression analysis. Results. Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 15 (3%) patients developed de novo IBD post-Ltx. The median duration of IBD was 15 (0-50) years at the time of Ltx and follow-up after Ltx was 5 (0-20) years. Ninety-one (25%) PSC-IBD patients developed colorectal neoplasia. The cumulative risk of colorectal neoplasia was higher after than before Ltx (HR: 1.9, 95% CI: 1.3-2.9, p = 0.002). A multivariate analysis demonstrated aminosalicylates and ursodeoxycholic acid as significantly associated with an increased risk of colorectal neoplasia post-Ltx. Duration and activity of IBD did not significantly affect the risk of neoplasia. Conclusion. The even higher risk of colorectal neoplasia in PSC-IBD patients after when compared with that of before Ltx underscores the importance of regular surveillance colonoscopies post-Ltx. The association of aminosalicylates and ursodeoxycholic acid to the development of colorectal neoplasia after Ltx should be further investigated. 相似文献
1000.
Carmona FD Gutala R Simeón CP Carreira P Ortego-Centeno N Vicente-Rabaneda E García-Hernández FJ García de la Peña P Fernández-Castro M Martínez-Estupiñán L Egurbide MV Tsao BP Gourh P Agarwal SK Assassi S Mayes MD Arnett FC Tan FK Martín J;Spanish Scleroderma Group 《Annals of the rheumatic diseases》2012,71(1):114-119