全文获取类型
收费全文 | 752篇 |
免费 | 72篇 |
国内免费 | 1篇 |
出版年
2023年 | 5篇 |
2022年 | 9篇 |
2021年 | 11篇 |
2020年 | 6篇 |
2019年 | 18篇 |
2018年 | 19篇 |
2017年 | 22篇 |
2016年 | 23篇 |
2015年 | 39篇 |
2014年 | 49篇 |
2013年 | 48篇 |
2012年 | 72篇 |
2011年 | 51篇 |
2010年 | 41篇 |
2009年 | 30篇 |
2008年 | 44篇 |
2007年 | 33篇 |
2006年 | 52篇 |
2005年 | 30篇 |
2004年 | 32篇 |
2003年 | 40篇 |
2002年 | 35篇 |
2001年 | 14篇 |
2000年 | 8篇 |
1999年 | 10篇 |
1998年 | 4篇 |
1997年 | 9篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1977年 | 2篇 |
1971年 | 3篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1961年 | 2篇 |
1960年 | 1篇 |
排序方式: 共有825条查询结果,搜索用时 609 毫秒
51.
Hurme K Gonzalez K Halvorsen M Foster B Moore D Chepko-Sade BD 《Journal of applied animal welfare science : JAAWS》2003,6(4):285-299
The Central Park Zoo, one of the Wildlife Conservation Society's Living Institutions in New York, recently renovated an exhibit for dart-poison frogs. Staff developed a new hollow coconut insect feeder in conjunction with this project. When the exhibit change, coconut feeder, and other enrichments were tested for effectiveness, the coconut feeder enrichment produced the greatest increase in frog activity in traditional and new exhibits. This may be due to the coconut feeder's relatively complicated nature, which randomizes the release of insects into the exhibit. The goal of this project was to help develop a best-practices approach to dendrobatid husbandry for zoological facilities to use in the future. 相似文献
52.
53.
Lehto K Tikkanen M Hiriart JB Paakkarinen V Aro EM 《Molecular plant-microbe interactions : MPMI》2003,16(12):1135-1144
The flavum strain of Tobacco mosaic virus (TMV) differs from the wild-type (wt) virus by causing strong yellow and green mosaic in the systemically infected developing leaves, yellowing in the fully expanded leaves, and distinct malformations of chloroplasts in both types of infected tissues. Analysis of the thylakoid proteins of flavum strain-infected tobacco leaves indicated that the chlorosis in mature leaves was accompanied by depletion of the entire photosystem II (PSII) core complexes and the 33-kDa protein of the oxygen evolving complex. The only change observed in the thylakoid proteins of the corresponding wt TMV-infected leaves was a slight reduction of the alpha and beta subunits of the ATP synthase complex. The coat proteins of different yellowing strains of TMV are known to effectively accumulate inside chloroplasts, but in this work, the viral movement protein also was detected in association with the thylakoid membranes of flavum strain-infected leaves. The mRNAs of different enzymes involved in the chlorophyll biosynthesis pathway were not reduced in the mature chlorotic leaves. These results suggest that the chlorosis was not caused by reduction of pigment biosynthesis, but rather, by reduction of specific proteins of the PSII core complexes and by consequent break-down of the pigments. 相似文献
54.
55.
Rho‐kinase inhibitor Y‐27632 increases cellular proliferation and migration in human foreskin fibroblast cells 下载免费PDF全文
Juha Piltti Markku Varjosalo Chengjuan Qu Jukka Häyrinen Mikko J. Lammi 《Proteomics》2015,15(17):2953-2965
The idea of direct differentiation of somatic cells into other differentiated cell types has attracted a great interest recently. Rho‐kinase inhibitor Y‐27632 (ROCKi) is a potential drug molecule, which has been reported to support the gene expressions typical for the chondrocytes, thus restricting their phenotypic conversion to fibroblastic cells upon the cellular expansion. In this study, we have investigated the short‐term biological responses of ROCKi to human primary foreskin fibroblasts. The fibroblast cells were exposed to 1 and 10 μM ROCKi treatments. A proteomics analysis revealed expression changes of 56 proteins, and a further protein pathway analysis suggested their association with the cell morphology, the organization, and the increased cellular movement and the proliferation. These functional responses were confirmed by a Cell‐IQ time‐lapse imaging analysis. Rho‐kinase inhibitor treatment increased the cellular proliferation up to twofold during the first 12 h, and a wound model based migration assay showed 50% faster filling of the mechanically generated wound area. Additionally, significantly less vinculin‐associated focal adhesions were present in the ROCKi‐treated cells. Despite the marked changes in the cell behavior, ROCKi was not able to induce the expression of the chondrocyte‐specific genes, such as procollagen α1(II) and aggrecan. 相似文献
56.
Antti T. Muuronen Mikko Taina Marja Hedman Jarkko Marttila Johanna Kuusisto Juha Onatsu Ritva Vanninen Pekka J?k?l? Petri Sipola Pirjo Mustonen 《PloS one》2015,10(3)
Purpose
The etiology of an ischemic stroke remains undetermined in 20–35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.Methods
Altogether 58 patients (mean age 57.7±10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered.Results
Mean VAT area was significantly higher in stroke patients (205±103 cm2 for men and 168±99 cm2 for women) compared to all reference populations (P<0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors.Conclusion
Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients. 相似文献57.
Miikka Tarkia Antti Saraste Christoffer Stark Tommi V?h?silta Timo Savunen Marjatta Strandberg Virva Saunavaara Tuula Tolvanen Jarmo Teuho Mika Ter?s Olli Mets?l? Petteri Rinne Ilkka Heinonen Nina Savisto Mikko Pietil? Pekka Saukko Anne Roivainen Juhani Knuuti 《PloS one》2015,10(6)
Objective
Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model.Methods
First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG).Results
Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4).Conclusions
We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques. 相似文献58.
Mikko O. Laukkanen Francesca Cammarota Tiziana Esposito Marco Salvatore Maria D. Castellone 《PloS one》2015,10(3)
Extracellular superoxide dismutase (SOD3), which catalyzes the dismutation of superoxide anions to hydrogen peroxide at the cell membranes, regulates the cellular growth in a dose-dependent manner. This enzyme induces primary cell proliferation and immortalization at low expression levels whereas it activates cancer barrier signaling through the p53-p21 pathway at high expression levels, causing growth arrest, senescence, and apoptosis. Because previous reports suggested that the SOD3–induced reduction in the rates of cellular growth and migration also occurred in the absence of functional p53 signaling, in the current study we investigated the SOD3-induced growth-suppressive mechanisms in anaplastic thyroid cancer cells. Based on our data, the robust over-expression of SOD3 increased the level of phosphorylation of the EGFR, ERBB2, RYK, ALK, FLT3, and EPHA10 receptor tyrosine kinases with the consequent downstream activation of the SRC, FYN, YES, HCK, and LYN kinases. However, pull-down experiments focusing on the small GTPase RAS, RAC, CDC42, and RHO revealed a reduced level of growth and migration signal transduction, such as the lack of stimulation of the mitogen pathway, in the SOD3 over-expressing cells, which was confirmed by MEK1/2 and ERK1/2 Western blotting analysis. Interestingly, the mRNA expression analyses indicated that SOD3 regulated the expression of guanine nucleotide-exchange factors (RHO GEF16, RAL GEF RGL1), GTPase-activating proteins (ARFGAP ADAP2, RAS GAP RASAL1, RGS4), and a Rho guanine nucleotide-disassociation inhibitor (RHO GDI 2) in a dose dependent manner, thus controlling signaling through the small G protein GTPases. Therefore, our current data may suggest the occurrence of dose-dependent SOD3–driven control of the GTP loading of small G proteins indicating a novel growth regulatory mechanism of this enzyme. 相似文献
59.
Otso Arponen Antti Muuronen Mikko Taina Petri Sipola Marja Hedman Pekka J?k?l? Ritva Vanninen Kari Pulkki Pirjo Mustonen 《PloS one》2015,10(4)
Background
Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.Methods
A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.Results
Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.Conclusion
IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology. 相似文献60.
Luning Wang Mikko J. Nissi Ferenc Tóth Jonah Shaver Casey P. Johnson Jinjin Zhang Michael Garwood Cathy S. Carlson Jutta M. Ellermann 《PloS one》2015,10(10)