全文获取类型
收费全文 | 319篇 |
免费 | 34篇 |
出版年
2022年 | 3篇 |
2021年 | 1篇 |
2020年 | 5篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 5篇 |
2015年 | 9篇 |
2014年 | 13篇 |
2013年 | 20篇 |
2012年 | 29篇 |
2011年 | 28篇 |
2010年 | 25篇 |
2009年 | 17篇 |
2008年 | 23篇 |
2007年 | 21篇 |
2006年 | 18篇 |
2005年 | 12篇 |
2004年 | 13篇 |
2003年 | 15篇 |
2002年 | 20篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1942年 | 1篇 |
排序方式: 共有353条查询结果,搜索用时 218 毫秒
81.
82.
Mirian F. Pimentel Ali Y. Srour Amanda J. Warner Jason P. Bond Carl A. Bradley John Rupe Martin I. Chilvers J. Alejandro Rojas Janette L. Jacobs Christopher R. Little Alison E. Robertson Loren J. Giesler Dean Malvick Kiersten Wise Albert Tenuta Ahmad M. Fakhoury 《Journal of applied microbiology》2022,132(5):3797-3811
83.
Zavitsanou K Nguyen V Greguric I Chapman J Ballantyne P Katsifis A 《Journal of molecular histology》2007,38(4):313-319
In the present study we aimed to establish an animal model of dexamethasone (DEX)-induced apoptosis in the thymus of rats.
The degree of apoptosis was determined in the same animals at 6 and 11 h after a single administration of DEX (5 mg/kg, ip)
by (a) in vivo biodistribution of the uptake of [123I]Annexin V, a biomarker of the early stages of apoptosis; (b) in vitro evaluation of the apoptotic index (percentage of number
of apoptotic cells versus total number of cells) in the form of DNA fragmentation, on tissue sections using in situ oligo
ligation (ISOL). ISOL demonstrated a 62- and 90-fold increase of apoptotic index at 6 and 11 h after DEX administration respectively,
in the outer part of the thymic lobule (cortex) and a 25- and 54-fold increases in the inner part of the thymic lobule (medulla)
in the corresponding treatment groups. In the biodistribution study, [123I]Annexin V uptake was significantly increased in the thymus of rats 11 h after DEX administration (by 1.3- to 1.4-fold) and
significantly decreased at the 6-h time point. We conclude that the specificity of the apoptotic signal provided by isotopic
methods in vivo would always require confirmation by complementary in vitro techniques that verify the assessment of ongoing
apoptosis accurately. 相似文献
84.
Lacrimal gland acinar cells are an important cell type to study due to their role in production and release of tear proteins,
a function essential for ocular surface integrity and normal visual acuity. However, mechanistic studies are often limited
by problems with transfection using either plasmid DNA or siRNA. Although various gene delivery methods are available, many
have been unproductive due to consistently low transfection efficiencies. We have developed a method using nucleofection that
can result in 50% transfection efficiency and 60% knockdown efficiency for plasmid DNA and siRNA, respectively. These results
are vastly improved relative to previous studies, demonstrating that nucleofection offers an efficient transfection technique
for primary lacrimal gland acinar cells. 相似文献
85.
Van Ly D Burgess JK Brock TG Lee TH Black JL Oliver BG 《American journal of physiology. Lung cellular and molecular physiology》2012,303(3):L239-L250
Eicosanoids are lipid-signaling mediators released by many cells in response to various stimuli. Increasing evidence suggests that eicosanoids such as leukotrienes and prostaglandins (PGs) may directly mediate remodeling. In this study, we assessed whether these substances could alter extracellular matrix (ECM) proteins and the inflammatory profiles of primary human airway smooth muscle cells (ASM) and fibroblasts. PGE(2) decreased both fibronectin and tenascin C in fibroblasts but only fibronectin in ASM. PGD(2) decreased both fibronectin and tenascin C in both ASM and fibroblasts, whereas PGF(2α) had no effect on ECM deposition. The selective PGI(2) analog, MRE-269, decreased fibronectin but not tenascin C in both cell types. All the PGs increased IL-6 and IL-8 release in a dose-dependent manner in ASM and fibroblasts. Changes in ECM deposition and cytokine release induced by prostaglandins in both ASM and fibroblasts were independent of an effect on cell number. Neither the acute nor repeated stimulation with leukotrienes had an effect on the deposition of ECM proteins or cytokine release from ASM or fibroblasts. We concluded that, collectively, these results provide evidence that PGs may contribute to ECM remodeling to a greater extent than leukotrienes in airway cells. 相似文献
86.
As a step toward understanding how community context shapes mating system evolution, we investigated the combined role of two plant antagonisms, vegetative herbivory and intraspecific competition, for reproduction and mating system expression (relative production of selfing, cleistogamous and facultatively outcrossing, chasmogamous flowers and fruits) of Impatiens capensis. In a survey of I. capensis populations, we found that vegetative herbivory and intraspecific competition were positively correlated. In a greenhouse experiment where leaf damage and plant density were manipulated, multispecies interactions had dramatic effects on reproductive and mating system traits. Despite having additive effects on growth, herbivory and competition had nonadditive effects for mating system expression, chasmogamous fruit production, flower number and size, and cleistogamous flower production. Our results demonstrate that competitive interactions influence the effect of herbivory (and vice versa) on fitness components and mating system, and thus antagonisms may have unforeseen consequences for mating system evolution, population genetic diversity, and persistence. 相似文献
87.
Pankhurst KL Mowat CG Rothery EL Hudson JM Jones AK Miles CS Walkinshaw MD Armstrong FA Reid GA Chapman SK 《The Journal of biological chemistry》2006,281(29):20589-20597
The mechanism for fumarate reduction by the soluble fumarate reductase from Shewanella frigidimarina involves hydride transfer from FAD and proton transfer from the active-site acid, Arg-402. It has been proposed that Arg-402 forms part of a proton transfer pathway that also involves Glu-378 and Arg-381 but, unusually, does not involve any bound water molecules. To gain further insight into the importance of this proton pathway we have perturbed it by substituting Arg-381 by lysine and methionine and Glu-378 by aspartate. Although all the mutant enzymes retain measurable activities, there are orders-of-magnitude decreases in their k(cat) values compared with the wild-type enzyme. Solvent kinetic isotope effects show that proton transfer is rate-limiting in the wild-type and mutant enzymes. Proton inventories indicate that the proton pathway involves multiple exchangeable groups. Fast scan protein-film voltammetric studies on wild-type and R381K enzymes show that the proton transfer pathway delivers one proton per catalytic cycle and is not required for transporting the other proton, which transfers as a hydride from the reduced, protonated FAD. The crystal structures of E378D and R381M mutant enzymes have been determined to 1.7 and 2.1 A resolution, respectively. They allow an examination of the structural changes that disturb proton transport. Taken together, the results indicate that Arg-381, Glu-378, and Arg-402 form a proton pathway that is completely conserved throughout the fumarate reductase/succinate dehydrogenase family of enzymes. 相似文献
88.
Ryan P. Wurz Liping H. Pettus Bradley Henkle Lisa Sherman Matthew Plant Kent Miner Helen J. McBride Lu Min Wong Christiaan J.M. Saris Matthew R. Lee Samer Chmait Christopher Mohr Faye Hsieh Andrew S. Tasker 《Bioorganic & medicinal chemistry letters》2010,20(5):1680-1684
A novel class of pyrazolopyridazine p38α mitogen-activated protein kinase (MAPK) inhibitors is disclosed. A structure activity relationship (SAR) investigation was conducted driven by the ability of these compounds to inhibit the p38α enzyme, the secretion of TNFα in a LPS-challenged THP1 cell line and TNFα-induced production of IL-8 in the presence of 50% human whole blood (hWB). This study resulted in the discovery of several inhibitors with IC50 values in the single-digit nanomolar range in hWB. Further investigation of the pharmacokinetic profiles of these lead compounds led to the identification of three potent and orally bioavailable p38α inhibitors 2h, 2m, and 13h. Inhibitor 2m was found to be highly selective for p38α/β over a panel of 402 other kinases in Ambit screening, and was highly efficacious in vivo in the inhibition of TNFα production in LPS-stimulated Lewis rats with an ED50 of ca. 0.08 mg/kg. 相似文献
89.
90.
Williams SJ Huang HH Kover K Moore W Berkland C Singh M Smirnova IV MacGregor R Stehno-Bittel L 《Organogenesis》2010,6(2):115-124
For people with type 1 diabetes and severe hypoglycemic unawareness, islet transplants offer hope for improving the quality of life. However, islet cell death occurs quickly during or after transplantation, requiring large quantities of islets per transplant. The purpose of this study was to determine whether poor function demonstrated in large islets was a result of diffusion barriers and if removing those barriers could improve function and transplantation outcomes. Islets were isolated from male DA rats and measured for cell viability, islet survival, glucose diffusion and insulin secretion. Modeling of diffusion barriers was completed using dynamic partial differential equations for a sphere. Core cell death occurred in 100% of the large islets (diameter >150 μm), resulting in poor survival within 7 days after isolation. In contrast, small islets (diameter <100 μm) exhibited good survival rates in culture (91%). Glucose diffusion into islets was tracked with 2-NBDG; 4.2 μm/min in small islets and 2.8 μm/min in large islets. 2-NBDG never permeated to the core cells of islets larger than 150 μm diameter. Reducing the diffusion barrier in large islets improved their immediate and long-term viability in culture. However, reduction of the diffusion barrier in large islets failed to improve their inferior in vitro insulin secretion compared to small islets, and did not return glucose control to diabetic animals following transplantation. Thus, diffusion barriers lead to low viability and poor survival for large islets, but are not solely responsible for the inferior insulin secretion or poor transplantation outcomes of large versus small islets. 相似文献