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101.
102.
Lukáš Kubala Hana Kolářová Jan Víteček Silvie Kremserová Anna Klinke Denise Lau Anna L.P. Chapman Stephan Baldus Jason P. Eiserich 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood.Methods
We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested.Results
MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed.Conclusions
Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins.General significance
Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins. 相似文献103.
104.
Christiane Guguen-Guillouzo Marie-France Szanjnert Denise Glaiser Claudine Gregori Fanny Schapira 《In vitro cellular & developmental biology. Plant》1981,17(5):369-377
Summary Aldolase and pyruvate kinase isozymes were investigated in cultured hepatocytes from fetal, regenerating, and 2-acetyl-aminofluorene-fed
rat liver as well as in some epithelial liver cell lines. Our results show that: (a) cell proliferation and prolonged expression
of specific isozymes were found only in cultured hepatocytes from 17-day old fetuses; (b) the fetal type of pyruvate kinase
expressed in regenerating and carcinogen-treated liver was temporarily lost only in cultured hepatocytes from regenerating
liver; (c) the adult type of aldolase and pyruvate kinase was absent in one epithelial cell line derived from a carcinogen-treated
liver and in the hepatoma tissue cell (HTC) line but was found in the Faza clone of the Reuber H35 cell line during the 50 first passages in vitro; and (d) the isozyme pattern of pyruvate kinase was always more strongly
shifted than that of aldolase.
The observations suggest that: (a) hepatocytes from carcinogen-treated liver exhibit the same lack of ability to proliferate
in primary culture as normal adult hepatocytes; (b) adult hepatocytes can produce fetal isozymes without prior cell division;
(c) pyruvate kinase is a stronger marker of dedifferentiation (retrodifferentiation) than aldolase; and (d) regulatory processes
of isozyme expression are different during ontogenesis, regeneration, and hepatocarcinogenesis.
This work was supported by the “Institut National de la Santé et de la Recherche Médicale” and the “Fondation pour la Recherche
Medicale Fran?aise” 相似文献
105.
Maria Azrad Kui Zhang Robin T. Vollmer John Madden Thomas J. Polascik Denise C. Snyder Mack T. Ruffin Judd W. Moul Dean Brenner Robert W. Hardy Wendy Demark-Wahnefried 《PloS one》2012,7(12)
Previous observational studies have reported associations between prostate cancer and alpha-linolenic acid (ALA). However, few investigations have been able to study this relationship prospectively and in well-controlled settings. Moreover, no studies have determined whether single nucleotide polymorphisms (SNPs) that influence ALA metabolism are associated with this common cancer. The purpose of this study was to explore associations between prostatic levels of ALA, SNPs and prostate cancer-specific biomarkers in samples collected from a previous randomized clinical trial conducted using a presurgical model and which tested the effects of flaxseed supplementation, a rich source of ALA, prior to prostatectomy (n = 134). Serum prostate-specific antigen (PSA) was determined and immunohistochemistry was used to assess tumor proliferation rate (Ki67). Prostatic ALA was determined with gas chromatography. Seven previously identified SNPs associated with delta-6 desaturase activity (rs99780, rs174537, rs174545, rs174572, rs498793, rs3834458 and rs968567) were tested for associations with prostatic ALA, PSA and Ki67. Despite consuming seven times more ALA per day, men in the flaxseed arm had similar amounts of prostatic ALA relative to men not consuming flaxseed. In unadjusted analysis, there were significant positive associations between prostatic ALA and PSA (ρ = 0.191, p = 0.028) and Ki67 (ρ = 0.186, p = 0.037). After adjusting for covariates (flaxseed, age, race, BMI and statin-use) the association between ALA and PSA remained (p = 0.004) but was slightly attenuated for Ki67 (p = 0.051). We did not observe associations between any of the SNPs studied and prostatic ALA; however, in models for PSA there was a significant interaction between rs498793 and ALA and for Ki67 there were significant interactions with ALA and rs99780 and rs174545. Independent and inverse associations were observed between rs174572 and Ki67. This study provides evidence that prostatic ALA, independent of the amount of ALA consumed, is positively associated with biomarkers of aggressive prostate cancer and that genetic variation may modify this relationship. 相似文献
106.
Sandhya Sankaranarayanan Margarita de la Llera-Moya Denise Drazul-Schrader Bela F. Asztalos Ginny L. Weibel George H. Rothblat 《Journal of lipid research》2010,51(11):3243-3249
Net flux of cholesterol represents the difference between efflux and influx and can result in net cell-cholesterol accumulation, net cell-cholesterol depletion, or no change in cellular cholesterol content. We measured radiolabeled cell-cholesterol efflux and cell-cholesterol mass using cholesterol-normal and -enriched J774 and elicited mouse peritoneal macrophage cells. Net cell-cholesterol effluxes were observed when cholesterol-enriched J774 cells were incubated with 3.5% apolipoprotein (apo) B depleted human serum, HDL3, and apo A-I. Net cell-cholesterol influxes were observed when cholesterol-normal J774 cells were incubated with the same acceptors except apo A-I. When incubated with 2.5% individual sera, cholesterol mass efflux in free cholesterol (FC)-enriched J774 cells correlated with the HDL-cholesterol (HDL-C) concentrations (r2 = 0.4; P=0.003), whereas cholesterol mass influx in cholesterol-normal J774 cells correlated with the LDL cholesterol (LDL-C) concentrations (r2 = 0.6; P<0.0001) of the individual sera. A positive correlation was observed between measurements of [3H]cholesterol efflux and reductions in cholesterol mass (r2 = 0.4; P=0.001) in FC-enriched J774 cells. In conclusion, isotopic efflux measurements from cholesterol-normal or cholesterol-enriched cells provide an accurate measurement of relative ability of an acceptor to remove labeled cholesterol under a specific set of experimental conditions, i.e., efflux potential. Moreover, isotopic efflux measurements can reflect changes in cellular cholesterol mass if the donor cells are enriched with cholesterol. 相似文献
107.
Ronan A. Lyons Denise Kendrick Elizabeth M. L. Towner Carol Coupland Mike Hayes Nicola Christie Judith Sleney Sarah Jones Richard Kimberlee Sarah E. Rodgers Samantha Turner Mariana Brussoni Yana Vinogradova Tinnu Sarvotham Steven Macey 《PloS one》2013,8(4)
Objective
To determine whether advocacy targeted at local politicians leads to action to reduce the risk of pedestrian injury in deprived areas.Design
Cluster randomised controlled trial.Setting
239 electoral wards in 57 local authorities in England and Wales.Participants
617 elected local politicians.Interventions
Intervention group politicians were provided with tailored information packs, including maps of casualty sites, numbers injured and a synopsis of effective interventions.Main outcome measures
25–30 months post intervention, primary outcomes included: electoral ward level: percentage of road traffic calmed; proportion with new interventions; school level: percentage with 20 mph zones, Safe Routes to School, pedestrian training or road safety education; politician level: percentage lobbying for safety measures. Secondary outcomes included politicians’ interest and involvement in injury prevention, and facilitators and barriers to implementation.Results
Primary outcomes did not significantly differ: % difference in traffic calming (0.07, 95%CI: −0.07 to 0.20); proportion of schools with 20 mph zones (RR 1.47, 95%CI: 0.93 to 2.32), Safe Routes to School (RR 1.34, 95%CI: 0.83 to 2.17), pedestrian training (RR 1.23, 95%CI: 0.95 to 1.61) or other safety education (RR 1.16, 95%CI: 0.97 to 1.39). Intervention group politicians reported greater interest in child injury prevention (RR 1.09, 95%CI 1.03 to 1.16), belief in potential to help prevent injuries (RR 1.36, 95%CI 1.16 to 1.61), particularly pedestrian safety (RR 1.55, 95%CI 1.19 to 2.03). 63% of intervention politicians reported supporting new pedestrian safety schemes. The majority found the advocacy information surprising, interesting, effectively presented, and could identify suitable local interventions.Conclusions
This study demonstrates the feasibility of an innovative approach to translational public health by targeting local politicians in a randomised controlled trial. The intervention package was positively viewed and raised interest but changes in interventions were not statistically significance. Longer term supported advocacy may be needed.Trial Registration
Current Controlled Trials ISRCTN91381117 相似文献108.
Denise Montgomery 《Arts Education Policy Review》2017,118(1):1-18
ABSTRACTCreative youth development (CYD) is a dynamic area of community arts education that successfully bridges youth development and arts education. CYD is an intentional, holistic practice that combines hands-on artmaking and skill building in the arts with development of life skills to support young people in successfully participating in adolescence and navigating into adulthood. Young people in CYD programs exhibit high levels of artistic skill and accomplishment along with increased self-esteem and sense of belonging. CYD participants are immersed in a broad array of rigorous artistic endeavors, including creating documentary films, researching and reporting on community issues through radio broadcasts, writing and staging new theatrical works, and engaging in thoughtful critique of one another's visual art work. The impact for youth of program participation extends beyond pride in artistic accomplishment. Throughout the United States, teen participants in CYD programs assert that the programs saved their lives, putting them on positive trajectories and away from gangs, drug use, crime, and ennui. This article provides a definition for the term creative youth development, describes core characteristics of CYD programs, and briefly describes four CYD programs. It provides background on the origins and history of creative youth development, including current advances in the field and signs the field is coalescing. The article describes creative youth development in the larger contexts of arts education and of education reform. Lastly, the article discusses policy, funding, and research needs and opportunities and provides questions for consideration. 相似文献
109.
110.
Gaware R Khunt R Czollner L Stanetty C Da Cunha T Kratschmar DV Odermatt A Kosma P Jordis U Classen-Houben D 《Bioorganic & medicinal chemistry》2011,19(6):1866-1880
Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and type 2. Whereas inhibition of 11β-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11β-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11β-HSD2. The most potent and selective compound is active against human 11β-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11β-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11β-HSD1 and 11β-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11β-HSD2 in the lower nanomolar range with up to 3600-fold selectivity. 相似文献