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181.
Peiying Pai Bharath Kumar Velmurugan Chia-Hua Kuo Chung-Yi Yen Tsung-Jung Ho Yueh-Min Lin Yu-Feng Chen Chao-Hung Lai Cecilia Hsuan Day Chih-Yang Huang 《Molecular and cellular biochemistry》2017,425(1-2):181-189
The objective of this study was to evaluate the effects of different protocols (P1, P2, and P3) of boldenone undecylenate (BU) and stanozolol (ST) on markers of liver and kidney function and variables of oxidative stress in these organs. For this, 54 male Wistar rats were divided into nine groups of six animals each. Each animal received intramuscularly 5.0 mg kg?1 of BU or ST once a week for 4 weeks (P1); 2.5 mg kg?1 of BU or ST once a week for 8 weeks (P2); and 1.25 mg kg?1 of BU or ST once a week for 12 weeks (P3). For each protocol, a control group was used, and they received 0.1 ml of olive oil intramuscularly. Blood and fragments of liver and kidney were collected for alanine aminotransferase activity (ALT), alkaline phosphatase, albumin, creatinine, cholesterol, total protein, triglycerides, urea, reactive oxygen species, thiobarbituric acid reactive substances, total thiols, and glutathione evaluation. The results show that the BU in doses of 5 (day 30) and 2.5 mg kg?1 (day 60) changes the ALT seric activity, possibly showing a hepatotoxic effect. High doses of BU may lead to increased levels of cholesterol (protocol P1) possibly due to inhibition of the normal steroid biosynthesis process. All protocols used caused changes in the redox balance of the organs studied (except in the liver, protocol P2), which indicates that these drugs might be harmful even at low doses. 相似文献
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183.
Lioubov I. Brueggemann Bharath K. Mani Jennifer Haick Kenneth L. Byron 《Journal of visualized experiments : JoVE》2012,(67)
Contraction or relaxation of smooth muscle cells within the walls of resistance arteries determines the artery diameter and thereby controls flow of blood through the vessel and contributes to systemic blood pressure. The contraction process is regulated primarily by cytosolic calcium concentration ([Ca2+]cyt), which is in turn controlled by a variety of ion transporters and channels. Ion channels are common intermediates in signal transduction pathways activated by vasoactive hormones to effect vasoconstriction or vasodilation. And ion channels are often targeted by therapeutic agents either intentionally (e.g. calcium channel blockers used to induce vasodilation and lower blood pressure) or unintentionally (e.g. to induce unwanted cardiovascular side effects).Kv7 (KCNQ) voltage-activated potassium channels have recently been implicated as important physiological and therapeutic targets for regulation of smooth muscle contraction. To elucidate the specific roles of Kv7 channels in both physiological signal transduction and in the actions of therapeutic agents, we need to study how their activity is modulated at the cellular level as well as evaluate their contribution in the context of the intact artery.The rat mesenteric arteries provide a useful model system. The arteries can be easily dissected, cleaned of connective tissue, and used to prepare isolated arterial myocytes for patch clamp electrophysiology, or cannulated and pressurized for measurements of vasoconstrictor/vasodilator responses under relatively physiological conditions. Here we describe the methods used for both types of measurements and provide some examples of how the experimental design can be integrated to provide a clearer understanding of the roles of these ion channels in the regulation of vascular tone. 相似文献
184.
Soraya M Kazuma Marcela F Cavalcante Andréia ER Telles Andrea Queiroz Maranh?o Dulcineia SP Abdalla 《MABS-AUSTIN》2013,5(5):763-775
The in vivo modified forms of low-density lipoprotein (LDL) are important for the formation of foam cells and as mediators of the immuno-inflammatory process involved in the progression of atherosclerosis. Electronegative LDL, LDL(-), is a LDL subfraction with pro-inflammatory properties that is present in human blood. To investigate possible atheroprotective effects, an anti-LDL(-) single-chain variable fragment (scFv) was expressed in the methylotrophic yeast Pichia pastoris and its activity was evaluated in vitro against macrophages and in experimental atherosclerosis in Ldlr-/- mice. The recombinant 2C7 scFv was produced in a yield of 9.5 mg of protein/L. The specificity and affinity of purified 2C7 scFv against LDL(-) was confirmed by ELISA. To assess the activity of 2C7 scFv on foam cell formation, RAW 264.7 macrophages were exposed to LDL(-) in the presence or absence of 2C7 scFv. The 2C7 scFv inhibited the uptake of LDL(-) by macrophages in a dose-dependent manner, and internalization of LDL(-) by these cells was found to be mediated by the CD36 and CD14 receptor. In addition, compared with untreated cells, lipid accumulation in macrophages was decreased, and the expression of Cd36, Tlr-4 and Cox-2 was downregulated in macrophages treated with 2C7 scFv. Importantly, compared with untreated mice, the treatment of Ldlr-/- mice with 2C7 scFv decreased the atherosclerotic lesion area at the aortic sinus. In conclusion, our data show that 2C7 scFv inhibits foam cell formation and atherosclerotic plaque development by modulating the expression of genes relevant to atherogenesis. These results encourage further use of this antibody fragment in the development of new therapeutic strategies that neutralize the pro-atherogenic effects of LDL(-). 相似文献
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186.
Bharath Srinivasan Sam Tonddast-Navaei Jeffrey Skolnick 《Bioorganic & medicinal chemistry letters》2017,27(17):4133-4139
Traditional structure and ligand based virtual screening approaches rely on the availability of structural and ligand binding information. To overcome this limitation, hybrid approaches were developed that relied on extraction of ligand binding information from proteins sharing similar folds and hence, evolutionarily relationship. However, they cannot target a chosen pocket in a protein. To address this, a pocket centric virtual ligand screening approach is required. Here, we employ a new, iterative implementation of a pocket and ligand-similarity based approach to virtual ligand screening to predict small molecule binders for the olfactomedin domain of human myocilin implicated in glaucoma. Small-molecule binders of the protein might prevent the aggregation of the protein, commonly seen during glaucoma. First round experimental assessment of the predictions using differential scanning fluorimetry with myoc-OLF yielded 7 hits with a success rate of 12.7%; the best hit had an apparent dissociation constant of 99 nM. By matching to the key functional groups of the best ligand that were likely involved in binding, the affinity of the best hit was improved by almost 10,000 fold from the high nanomolar to the low picomolar range. Thus, this study provides preliminary validation of the methodology on a medically important glaucoma associated protein. 相似文献
187.
Sery Gonedelé Bi Didier P Sokouri Kouakou Tiékoura Oulo Alla N?Nan Marcel Lolo Félix Gnangbé Assanvo SP N?Guetta 《Bioinformation》2014,10(11):671-678
Cête d׳Ivoire continues to have the highest HIV-1 prevalence rate in West Africa, although the infection number is in constant
decline. The external envelope protein of the viruses is a likely site of selection, and responsible for receptor binding and entry into
host cells, and therefore constitutes an ideal region with which to investigate the evolutionary processes acting on HIV-1. In this
study, we analyse 189 envelope glycoprotein V3 loop region sequences of viruse isolates from 1995 to 2009, from HIV-1 untreated
patients living in Cête d׳Ivoire, to decipher the temporal relationship between disease diversity, divergence and selection. Our
analyses show that the nonsynonymous and synonymous ratio (dN/dS) was lower than 1 for viral populations analysed within 15
years, which showed the sequences did not undergo adequate immune pressure. The phylogenetic tree of the sequences analysed
demonstrated distinctly long internal branches and short external branches, suggesting that only a small number of viruses
infected the new host cell at each transmission. In addition to identifying sites under purifying selection, we also identified neutral
sites that can cause false positive inference of selection. These sites presented form a resource for future studies of selection
pressures acting on HIV-1 enν gene in Cête d׳Ivoire and other West African countries. 相似文献
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190.
Human clinical and psychophysical observations suggest that the taste
system is able to compensate for losses in peripheral nerve input, since
patients do not commonly report decrements in whole mouth taste following
chorda tympani nerve damage or anesthesia. Indeed, neurophysiological data
from the rat nucleus of the solitary tract (NST) suggests that a release of
inhibition (disinhibition) may occur centrally following chorda tympani
nerve anesthesia. Our purpose was to study this possibility further. We
recorded from 59 multi- and single- unit taste-responsive sites in the rat
NST before, during and after recovery from chorda tympani nerve anesthesia.
During anesthesia, average anterior tongue responses were eliminated but no
compensatory increases in palatal or posterior tongue responses were
observed. However, six individual sites displayed increased taste
responsiveness during anesthesia. The average increase was 32.9%.
Therefore, disinhibition of taste responses was observed, but infrequently
and to a small degree in the NST At a subset of sites, chorda
tympani-mediated responses decreased while greater superficial
petrosal-mediated responses remained the same during anesthesia. Since this
effect was accompanied by a decrease in spontaneous activity, we propose
that taste compensation may result in part by a change in signal-to-noise
ratio at a subset of sites.
相似文献