全文获取类型
收费全文 | 1364篇 |
免费 | 89篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 33篇 |
妇产科学 | 21篇 |
基础医学 | 176篇 |
口腔科学 | 32篇 |
临床医学 | 184篇 |
内科学 | 249篇 |
皮肤病学 | 16篇 |
神经病学 | 168篇 |
特种医学 | 34篇 |
外科学 | 142篇 |
综合类 | 5篇 |
一般理论 | 1篇 |
预防医学 | 192篇 |
眼科学 | 12篇 |
药学 | 122篇 |
中国医学 | 4篇 |
肿瘤学 | 62篇 |
出版年
2023年 | 9篇 |
2022年 | 17篇 |
2021年 | 22篇 |
2020年 | 26篇 |
2019年 | 37篇 |
2018年 | 35篇 |
2017年 | 56篇 |
2016年 | 42篇 |
2015年 | 39篇 |
2014年 | 37篇 |
2013年 | 69篇 |
2012年 | 102篇 |
2011年 | 93篇 |
2010年 | 53篇 |
2009年 | 54篇 |
2008年 | 86篇 |
2007年 | 100篇 |
2006年 | 94篇 |
2005年 | 94篇 |
2004年 | 77篇 |
2003年 | 70篇 |
2002年 | 57篇 |
2001年 | 10篇 |
2000年 | 11篇 |
1999年 | 4篇 |
1998年 | 10篇 |
1997年 | 15篇 |
1996年 | 13篇 |
1995年 | 10篇 |
1994年 | 9篇 |
1993年 | 9篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 8篇 |
1974年 | 3篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1967年 | 2篇 |
1966年 | 6篇 |
排序方式: 共有1455条查询结果,搜索用时 15 毫秒
241.
Denstadli V Bakke AM Berge GM Krogdahl A Hillestad M Holm H Ruyter B 《The Journal of nutrition》2011,141(9):1618-1628
An increasingly larger proportion of the oils used in diets for farmed fish are plant derived and rapeseed oil is most commonly used. Despite high dietary lipid levels and a marked change in lipid composition, the transport and metabolic fate of absorbed fatty acids is not fully understood in teleost fish. The main purpose of this study was to trace the postabsorptive metabolic fate of 2 fatty acids of different chain length: oleic acid [(3)H-18:1(n-9)], constituting 70% of fatty acids in rapeseed oil, and the medium-chain decanoic acid [(14)C-10:0], which does not require carrier molecules for membrane passage. The fatty acids and their metabolites were traced in portal and peripheral blood, liver, heart, skeletal muscle, and visceral adipose tissue at time intervals from 3 to 48 h after feeding. The portal vein was the primary transport route for both 10:0 and 18:1(n-9) from the intestine to the liver the first 6 h after feed intake. From 12 to 48 h, the peripheral route became increasingly more important. The study also indicates a possible direct transport route of fatty acids from the intestine to the surrounding viscera. Our data demonstrate that whereas 18:1(n-9) is primarily deposited as TG in skeletal muscle and visceral adipose tissue, 10:0 is used by the heart and skeletal muscle as a source for rapid energy production. 相似文献
242.
O'Neill HM Maarbjerg SJ Crane JD Jeppesen J Jørgensen SB Schertzer JD Shyroka O Kiens B van Denderen BJ Tarnopolsky MA Kemp BE Richter EA Steinberg GR 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(38):16092-16097
AMP-activated protein kinase (AMPK) β1 or β2 subunits are required for assembling of AMPK heterotrimers and are important for regulating enzyme activity and cellular localization. In skeletal muscle, α2β2γ3-containing heterotrimers predominate. However, compensatory up-regulation and redundancy of AMPK subunits in whole-body AMPK α2, β2, and γ3 null mice has made it difficult to determine the physiological importance of AMPK in regulating muscle metabolism, because these models have normal mitochondrial content, contraction-stimulated glucose uptake, and insulin sensitivity. In the current study, we generated mice lacking both AMPK β1 and β2 isoforms in skeletal muscle (β1β2M-KO). β1β2M-KO mice are physically inactive and have a drastically impaired capacity for treadmill running that is associated with reductions in skeletal muscle mitochondrial content but not a fiber-type switch. Interestingly, young β1β2M-KO mice fed a control chow diet are not obese or insulin resistant but do have impaired contraction-stimulated glucose uptake. These data demonstrate an obligatory role for skeletal muscle AMPK in maintaining mitochondrial capacity and contraction-stimulated glucose uptake, findings that were not apparent in mice with single mutations or deletions in muscle α, β, or γ subunits. 相似文献
243.
Runa M. Grimholt Bente Fjeld Hilde Selsås Lutz Schwettmann Olav Klingenberg 《Hemoglobin》2019,43(2):122-125
244.
Notohamiprodjo M Pedersen M Glaser C Helck AD Lodemann KP Jespersen B Fischereder M Reiser MF Sourbron SP 《Journal of magnetic resonance imaging : JMRI》2011,34(3):595-607
Purpose:
To measure the systematic error in perfusion and filtration parameters derived from magnetic resonance (MR) renography caused by protein binding of MR contrast agents.Materials and Methods:
Eight healthy Danish Landrace pigs were examined with dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). In four pigs a bolus of gadopentetate‐dimeglumine (Gd‐DTPA; no protein binding) was injected, followed by gadobenate‐dimeglumine (Gd‐BOPTA; 10% protein binding). The order was reversed in the other four pigs. A two‐compartment filtration model was generalized to allow for protein binding and fitted to whole‐cortex region of interest (ROI) curves. Single‐kidney plasma flow and volume, tubular flow (or GFR), and tubular transit time of both agents were compared.Results:
The data show a strong systematic underestimation (P < 0.001) in GFR by Gd‐BOPTA (33 ± 7.2%), and no significant differences (P > 0.05) in plasma flow (2.2 ± 18%), plasma volume (?1.7 ± 7.8%) and tubular transit time (3.1 ± 7.2%). The order of injection had no significant effect.Conclusion:
Theory and experiments agree that perfusion parameters of both agents are comparable, whereas GFR is underestimated with Gd‐BOPTA due to the dependence of relaxivity on protein content. Hence, GFR cannot be measured with protein‐bound contrast agents, but the proposed dual‐agent protocol may produce new functional indices measuring protein filtration. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.245.
Høeg LD Sjøberg KA Jeppesen J Jensen TE Frøsig C Birk JB Bisiani B Hiscock N Pilegaard H Wojtaszewski JF Richter EA Kiens B 《Diabetes》2011,60(1):64-73
OBJECTIVE
We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance.RESEARCH DESIGN AND METHODS
Insulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg−1 · min−1).RESULTS
Intralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men (P < 0.05), and insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by intralipid.CONCLUSIONS
Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.Whole-body insulin resistance plays a major role in the pathogenesis of type 2 diabetes and has generally been related to high plasma concentrations of lipids. Intralipid infusion increases plasma lipid concentrations and has been used as a model to investigate lipid-induced insulin resistance in rodents (1,2) and humans (3–5). The studies uniformly demonstrate that intralipid infusion reduces whole-body insulin sensitivity markedly within 3–4 h. Various mechanisms have been suggested to explain this phenomenon, including lipid-induced interaction with proximal insulin-signaling capacity, accumulation of lipid intermediates, and inflammation (5). The classic lipid-induced inhibition of the insulin-signaling pathway has, however, been challenged in recent studies where insulin receptor substrate (IRS)-1 tyrosine phosphorylation, IRS-1–associated phosphatidylinositol (PI) 3-kinase activity, Akt, and AS160 phosphorylation were unaltered after 2- to 6-h intralipid infusion in rats (1) and in lean (6) and obese (7) men.Only one of the human studies included women and, in that study, a matching of sexes with respect to important matching criteria (i.e., aerobic fitness levels) was not performed (8). In a rodent study, 2 h of intralipid infusion reduced insulin-stimulated whole-body glucose uptake in male rats but not in females rats (9) and, in accordance, phosphorylation of IRS-1 and PI 3-kinase activity was reduced only in male rats (9). We have previously reported that women have greater insulin-stimulated whole-body and leg glucose uptake than matched men despite higher intramyocellular triacylglycerol (IMTG) concentration (10). Also, women have higher muscle mRNA levels of several proteins involved in muscle lipid metabolism including fatty acid translocase/CD36 (FAT/CD36), membrane-bound fatty acid–binding protein (FABPpm), cytosolic fatty acid–binding protein (FABPc), lipoprotein lipase (11), and a higher percentage of myosin heavy chain type 1 muscle fibers (10,12,13). Therefore, the aims of this study were 1) to test the hypothesis that women are less prone to intralipid-induced insulin resistance on a whole-body level and in skeletal muscle than men and 2) to investigate the molecular mechanisms responsible for the intralipid-induced decrease in insulin sensitivity. 相似文献246.
247.
Andersen GØ Ueland T Knudsen EC Scholz H Yndestad A Sahraoui A Smith C Lekva T Otterdal K Halvorsen B Seljeflot I Aukrust P 《Diabetes》2011,60(5):1544-1551
OBJECTIVE
On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI).RESEARCH DESIGN AND METHODS
Activin A measurement and oral glucose tolerance tests (OGTTs) were performed in patients (n = 115) with acute MI, without previously known diabetes, and repeated after 3 months. Release of activin A and potential anti-inflammatory effects of activin A were measured in human endothelial cells. Activin A effects on insulin secretion and inflammation were tested in human pancreatic islet cells.RESULTS
1) In patients with acute MI, serum levels of activin A were significantly higher in those with abnormal glucose regulation (AGR) compared with those with normal glucose regulation. Activin A levels were associated with the presence of AGR 3 months later (adjusted odds ratio 5.1 [95% CI 1.73–15.17], P = 0.003). 2) In endothelial cells, glucose enhanced the release of activin A, whereas activin A attenuated the release of interleukin (IL)-8 and enhanced the mRNA levels of the antioxidant metallothionein. 3) In islet cells, activin A attenuated the suppressive effect of inflammatory cytokines on insulin release, counteracted the ability of these inflammatory cytokines to induce mRNA expression of IL-8, and induced the expression of transforming growth factor-β.CONCLUSIONS
We found a significant association between activin A and newly detected AGR in patients with acute MI. Our in vitro findings suggest that this association represents a counteracting mechanism to protect against inflammation, hyperglycemia, and oxidative stress.Type 2 diabetes is a chronic disease with rapidly increasing prevalence, and patients with type 2 diabetes have an increased risk of developing coronary artery disease (CAD) (1,2). The coexistence of type 2 diabetes and CAD is considerable, and type 2 diabetes has been rated as an equivalent of CAD. In contrast, many patients with established CAD have type 2 diabetes or its pre-states (3). Thus, a high prevalence of impaired glucose tolerance (IGT) and unknown type 2 diabetes has been reported in patients with CAD with no previous diagnosis of diabetes (4–6). Abnormal glucose regulation (AGR) (impaired fasting glucose [IFG], IGT, or type 2 diabetes) is approximately twice as common among patients with myocardial infarction (MI) as in population-based controls (7), and the presence of AGR is a strong risk factor for new cardiovascular events after acute MI (3,8,9).The association between cardiovascular disease and hyperglycemia may be explained by an accumulation of cardiovascular risk factors associated with the metabolic syndrome in patients with AGR (10). It may, however, also relate to mechanisms triggered by hyperglycemia and insulin resistance leading to cardiovascular damage before the onset of overt diabetes (7,11). Moreover, experimental and clinical data have illuminated a role of inflammation in atherogenesis, and it has been suggested that atherosclerosis, type 2 diabetes, and the metabolic syndrome are multifactorial diseases characterized by chronic inflammation (12). However, the reasons for the association between AGR and atherosclerotic disorders are not fully understood.Activin A, a member of the transforming growth factor (TGF)-β superfamily (13), has been recognized as a multifunctional cytokine with roles in regulation of wound repair, cell differentiation, and inflammation, and growing evidence implicates a role for activin A in inflammatory disorders potentially mediating both inflammatory and anti-inflammatory effects (14). Activin A also has been suggested to be important for glucose homeostasis, at least partly through direct stimulatory effects on pancreatic β-cells (15). However, reports on activin A levels in patients with type 2 diabetes are few and include a small number of patients (16,17). Furthermore, there are only a few reports on activin A levels during acute coronary syndrome (ACS) and no reports on patients with ST-elevation MI (STEMI) exclusively. Moreover, no data exist on the association between activin A and AGR in patients with CAD.On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucose abnormalities associated with STEMI, potentially representing a counteracting mechanism in response to AGR. This hypothesis was investigated by different approaches, including studies in a well-characterized population with STEMI and experimental studies in endothelial cells and pancreatic β-cells. 相似文献248.
249.
Binding of peptides to HLA-DQ molecules: peptide binding properties of the disease-associated HLA-DQ({alpha}1*0501, {beta}1*0201) molecule 总被引:2,自引:0,他引:2
Johansen Bente H.; Buus Soren; Vartdal Frode; Viken Helge; Eriksen Jon A.; Thorsby Erik; Sollid Ludvig M. 《International immunology》1994,6(3):453-461
Peptide binding to DQ molecules has not previously been described.Here we report a biochemical peptlde-blndlng assay specificfor the BQ2 [I.e. DQ(1*0501, ß1*0201)] molecule. Thismolecule was chosen since It shows a strong association to diseasessuch as celiac disease and insulin-dependent diabetes mellitus.Initially we radlolabelled some selected peptides and testedthem for binding to affinity-purified DQ2 molecules. One ofthe peptides, a Mycobacterium bovis (MB) 65 kDa 243–255Ypeptide, displayed a good slgnal-to-noise ratio and was thuschosen as an indicator peptide in the DQ2 binding assay. TheMB 65 kDa 243–255Y peptide bound to DQ2 In a strictlypH-dependent fashion, with optimal binding around pH 5 and onlyweak binding at pH 7.4. The association of the MB 65 kDa 243–255Ypeptide to DQ2 was slow, but once formed, the peptide-HLA complexeswere very stable. The binding of peptides to DQ2 was specific,as shown in Inhibition experiments with a panel of 47 peptides,differing in length, sequence, and origin. The binding of peptidesto DR3 was tested in a similar assay with a Mycobacterium tuberculosis65 kDa 3–13 peptide as the binding indicator. DQ2 andDR3 molecules bound to different sets of peptides. However,the peptide binding to DQ2 and DR3 showed, In general, similarcharacteristics with respect to pH dependence and kinetic parameters,Indicating that the overall rules for peptide binding to DQmolecules are the same as those previously shown for human DRand murlne I-A and I-E molecules. 相似文献
250.
Hansen PS Jensen TG Gahrn-Hansen B 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2005,113(3):229-231
Dysgonomonas capnocytophagoides, formerly known as CDC group DF-3, is an opportunistic pathogen associated with diarrhoea and very rarely bacteraemia. We report a case of D. capnocytophagoides found in blood cultures from a severely neutropenic patient treated for acute myeloid leukaemia. The isolate was found resistant to penicillin, cephalosporins, meropenem, aminoglycosides and ciprofloxacin, and susceptible to ampicillin, tetracycline, chloramphenicol, clindamycin and trimethoprim-sulphamethoxazole. It was identified using conventional phenotypic testing but remained unidentified by the automated identification system (Vitek-2) as this system did not contain DF-3 or D. capnocytophagoides in its database. 相似文献