全文获取类型
收费全文 | 152篇 |
免费 | 7篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 8篇 |
2013年 | 11篇 |
2012年 | 13篇 |
2011年 | 19篇 |
2010年 | 6篇 |
2009年 | 3篇 |
2008年 | 6篇 |
2007年 | 7篇 |
2006年 | 9篇 |
2005年 | 6篇 |
2004年 | 6篇 |
2003年 | 3篇 |
2002年 | 6篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1986年 | 3篇 |
1983年 | 2篇 |
1970年 | 2篇 |
1965年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有159条查询结果,搜索用时 15 毫秒
151.
Mehner Thomas Rapp Tobias Monk Christopher T. Beck Mara E. Trudeau Ashley Kiljunen Mikko Hilt Sabine Arlinghaus Robert 《Ecosystems》2019,22(2):346-362
Ecosystems - It is well documented that aquatic ecosystems may be subsidized by naturally derived terrestrial carbon sources. In contrast, the intentional or unintentional subsidy of animal... 相似文献
152.
153.
154.
155.
At an identified neuro-neuronal synapse of the buccal ganglion of Aplysia, quantal release of acetylcholine (ACh) is increased by FMRFamide and decreased by histamine or buccalin. Activation of presynaptic receptors for these neuromodulators modifies a presynaptic Ca2+ current which is nifedipine-resistant and omega-conotoxin-sensitive. The voltage-sensitivity of these N-type Ca2+ channels is increased by FMRFamide and decreased by histamine through the intermediate of G proteins. Buccalin does not implicate G proteins and reduces the Ca2+ current without affecting the voltage-sensitivity of N-type Ca2+ channels. The possibility of relating the shifts in voltage-dependence of the Ca2+ current induced by FMRFamide and histamine to the phosphorylation state of the N-type Ca2+ channels is discussed. A scheme for the complex regulation of ACh release by presynaptic auto- and heteroreceptors is proposed. 相似文献
156.
Filsy Samuel William P. Flavin Sobia Iqbal Consiglia Pacelli Sri Dushyaanthan Sri Renganathan Louis-Eric Trudeau Edward M. Campbell Paul E. Fraser Anurag Tandon 《The Journal of biological chemistry》2016,291(9):4374-4385
Although trace levels of phosphorylated α-synuclein (α-syn) are detectable in normal brains, nearly all α-syn accumulated within Lewy bodies in Parkinson disease brains is phosphorylated on serine 129 (Ser-129). The role of the phosphoserine residue and its effects on α-syn structure, function, and intracellular accumulation are poorly understood. Here, co-expression of α-syn and polo-like kinase 2 (PLK2), a kinase that targets Ser-129, was used to generate phosphorylated α-syn for biophysical and biological characterization. Misfolding and fibril formation of phosphorylated α-syn isoforms were detected earlier, although the fibrils remained phosphatase- and protease-sensitive. Membrane binding of α-syn monomers was differentially affected by phosphorylation depending on the Parkinson disease-linked mutation. WT α-syn binding to presynaptic membranes was not affected by phosphorylation, whereas A30P α-syn binding was greatly increased, and A53T α-syn was slightly lower, implicating distal effects of the carboxyl- on amino-terminal membrane binding. Endocytic vesicle-mediated internalization of pre-formed fibrils into non-neuronal cells and dopaminergic neurons matched the efficacy of α-syn membrane binding. Finally, the disruption of internalized vesicle membranes was enhanced by the phosphorylated α-syn isoforms, a potential means for misfolded extracellular or lumenal α-syn to access cytosolic α-syn. Our results suggest that the threshold for vesicle permeabilization is evident even at low levels of α-syn internalization and are relevant to therapeutic strategies to reduce intercellular propagation of α-syn misfolding. 相似文献
157.
Epitope mapping and targeted quantitation of the cardiac biomarker troponin by SID‐MRM mass spectrometry 下载免费PDF全文
Cheng Zhao Beth Trudeau Helen Xie John Prostko Jeffrey Fishpaugh Carol Ramsay 《Proteomics》2014,14(11):1311-1321
The absolute quantitation of the targeted protein using MS provides a promising method to evaluate/verify biomarkers used in clinical diagnostics. In this study, a cardiac biomarker, troponin I (TnI), was used as a model protein for method development. The epitope peptide of TnI was characterized by epitope excision followed with LC/MS/MS method and acted as the surrogate peptide for the targeted protein quantitation. The MRM‐based MS assay using a stable internal standard that improved the selectivity, specificity, and sensitivity of the protein quantitation. Also, plasma albumin depletion and affinity enrichment of TnI by anti‐TnI mAb‐coated microparticles reduced the sample complexity, enhanced the dynamic range, and further improved the detecting sensitivity of the targeted protein in the biological matrix. Therefore, quantitation of TnI, a low abundant protein in human plasma, has demonstrated the applicability of the targeted protein quantitation strategy through its epitope peptide determined by epitope mapping method. 相似文献
158.
Niladri Basu Anton M. Scheuhammer Kirsti Rouvinen-Watt R. Douglas Evans Vance L. Trudeau Laurie H.M. Chan 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2010,151(3):379-385
The effects of mercury (Hg) on key components of the GABAergic system were evaluated in discrete brain regions of captive juvenile male American mink (Neovison vison) using in vitro and in vivo (whole animal) experimental approaches. In vitro studies on cortical brain tissues revealed that inorganic Hg (HgCl2; IC50 = 0.5 ± 0.2 µM) and methyl Hg (MeHgCl; IC50 = 1.6 ± 0.2 µM) inhibited glutamic acid decarboxylase (GAD; EC 4.1.1.15) activity. There were no Hg-related effects on [3H]-muscimol binding to GABA(A) receptors (IC50s > 100 µM). HgCl2 (IC50 = 0.8 ± 0.3 µM) but not MeHgCl (IC50 > 100 µM) inhibited GABA-transaminase (GABA-T; EC 2.6.1.19) activity. In a whole animal study, neurochemical indicators of GABAergic function were measured in brain regions (occipital cortex, cerebellum, brain stem, and basal ganglia) of captive mink fed relevant levels of MeHgCl (0 to 2 µg/g feed, ppm) daily for 89 d. No effects on GAD activity were measured. Concentration-dependent decreases in [3H]-muscimol binding to GABA(A) receptors and GABA-T activity were found in several brain regions, with reductions as great as 94% (for GABA(A) receptor levels) and 71% (for GABA-T activity) measured in the brain stem and basal ganglia. These results show that chronic exposure to environmentally relevant levels of MeHg disrupts GABAergic signaling. Given that GABA is the main inhibitory neurotransmitter in the mammalian nervous system, prolonged disruptions of its function may underlie the sub-clinical impacts of MeHg at relevant levels to animal health. 相似文献
159.
Omar Falou Ali Sadeghi-Naini Sameera Prematilake Ervis Sofroni Naum Papanicolau Sara Iradji Zahra Jahedmotlagh Sharon Lemon-Wong Jean-Philippe Pignol Eileen Rakovitch Judit Zubovits Jacqueline Spayne Rebecca Dent Maureen Trudeau Jean Francois Boileau Frances C Wright Martin J Yaffe Gregory J Czarnota 《Translational oncology》2013,6(1):17-24
PURPOSE: Ultrasound elastography is a new imaging technique that can be used to assess tissue stiffness. The aim of this study was to investigate the potential of ultrasound elastography for monitoring treatment response of locally advanced breast cancer patients undergoing neoadjuvant therapy. METHODS: Fifteen women receiving neoadjuvant chemotherapy had the affected breast scanned before, 1, 4, and 8 weeks following therapy initiation, and then before surgery. Changes in elastographic parameters related to tissue biomechanical properties were then determined and compared to clinical and pathologic tumor response after mastectomy. RESULTS: Patients who responded to therapy demonstrated a significant decrease (P < .05) in strain ratios and strain differences 4 weeks after treatment initiation compared to non-responding patients. Mean strain ratio and mean strain difference for responders was 81 ± 3% and 1 ± 17% for static regions of interest (ROIs) and 81 ± 3% and 6 ± 18% for dynamic ROIs, respectively. In contrast, these parameters were 102±2%, 110±17%, 101±4%, and 109±30% for non-responding patients, respectively. Strain ratio using static ROIs was found to be the best predictor of treatment response, with 100% sensitivity and 100% specificity obtained 4 weeks after starting treatment. CONCLUSIONS: These results suggest that ultrasound elastography can be potentially used as an early predictor of tumor therapy response in breast cancer patients. 相似文献