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排序方式: 共有248条查询结果,搜索用时 31 毫秒
61.
Mustafa S See HB Seeber RM Armstrong SP White CW Ventura S Ayoub MA Pfleger KD 《The Journal of biological chemistry》2012,287(16):12952-12965
We have provided the first evidence for specific heteromerization between the α(1A)-adrenoceptor (α(1A)AR) and CXC chemokine receptor 2 (CXCR2) in live cells. α(1A)AR and CXCR2 are both expressed in areas such as the stromal smooth muscle layer of the prostate. By utilizing the G protein-coupled receptor (GPCR) heteromer identification technology on the live cell-based bioluminescence resonance energy transfer (BRET) assay platform, our studies in human embryonic kidney 293 cells have identified norepinephrine-dependent β-arrestin recruitment that was in turn dependent upon co-expression of α(1A)AR with CXCR2. These findings have been supported by co-localization observed using confocal microscopy. This norepinephrine-dependent β-arrestin recruitment was inhibited not only by the α(1)AR antagonist Terazosin but also by the CXCR2-specific allosteric inverse agonist SB265610. Furthermore, Labetalol, which is marketed for hypertension as a nonselective β-adrenoceptor antagonist with α(1)AR antagonist properties, was identified as a heteromer-specific-biased agonist exhibiting partial agonism for inositol phosphate production but essentially full agonism for β-arrestin recruitment at the α(1A)AR-CXCR2 heteromer. Finally, bioluminescence resonance energy transfer studies with both receptors tagged suggest that α(1A)AR-CXCR2 heteromerization occurs constitutively and is not modulated by ligand. These findings support the concept of GPCR heteromer complexes exhibiting distinct pharmacology, thereby providing additional mechanisms through which GPCRs can potentially achieve their diverse biological functions. This has important implications for the use and future development of pharmaceuticals targeting these receptors. 相似文献
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K. Barth C. Pfleger A. Linge J. A. Sim A. Surprenant N. Steinbronn R. H. Strasser M. Kasper 《Histochemistry and cell biology》2010,134(1):31-38
It has recently been shown in epithelial cells that the ATP-gated ion channel P2X7R is in part, associated with caveolae and
colocalized with caveolin-1. In the present study of the mouse heart, we show for the first time, using immunohistochemistry
and cryoimmunoelectron microscopy, that P2X7R is expressed in atrial cardiomyocytes and in cardiac microvascular endothelial
cells, but not in the ventricle cardiomyocytes. Furthermore, biochemical data indicate the presence of two forms of P2X7R,
the classical glycosylated 80 kDa isoform and a protein with the molecular weight of 56 kDa, in both cardiomyocytes and endothelial
cells of the mouse heart. The functionality of both proteins in heart cells is still unclear. In cardiac tissue homogenates
derived from caveolin-1 deficient mice (cav-1
−/−), an increase of the P2Xrx7 mRNA and P2X7R protein (80 kDa) was found, particularly in atrial samples. In addition, P2rx7
−/− mice showed enhanced protein levels of caveolin-1 in their atrial tissues. Although the details of cellular mechanisms that
underlie the relationship between caveolin-1 and P2X7R in atrial cardiomyocytes and the electrophysiological consequences
of the increased P2X7R expression in atrial cells of cav-1
−/− mice remain to be elucidated, the cardiomyopathy detectable in cav-1
−/− mice is possibly related to a disturbed crosstalk between P2X7R and caveolin-1 in different heart cell populations. 相似文献
65.
William W. Lockwood Raj Chari Bradley P. Coe Kelsie L. Thu Cathie Garnis Chad A. Malloff Jennifer Campbell Ariane C. Williams Dorothy Hwang Chang-Qi Zhu Timon P. H. Buys John Yee John C. English Calum MacAulay Ming-Sound Tsao Adi F. Gazdar John D. Minna Stephen Lam Wan L. Lam 《PLoS medicine》2010,7(7)
66.
Scott F. Heron Bette L. Willis William J. Skirving C. Mark Eakin Cathie A. Page Ian R. Miller 《PloS one》2010,5(8)
Coral reefs are under increasing pressure in a changing climate, one such threat being more frequent and destructive outbreaks of coral diseases. Thermal stress from rising temperatures has been implicated as a causal factor in disease outbreaks observed on the Great Barrier Reef, Australia, and elsewhere in the world. Here, we examine seasonal effects of satellite-derived temperature on the abundance of coral diseases known as white syndromes on the Great Barrier Reef, considering both warm stress during summer and deviations from mean temperatures during the preceding winter. We found a high correlation (r2 = 0.953) between summer warm thermal anomalies (Hot Snap) and disease abundance during outbreak events. Inclusion of thermal conditions during the preceding winter revealed that a significant reduction in disease outbreaks occurred following especially cold winters (Cold Snap), potentially related to a reduction in pathogen loading. Furthermore, mild winters (i.e., neither excessively cool nor warm) frequently preceded disease outbreaks. In contrast, disease outbreaks did not typically occur following warm winters, potentially because of increased disease resistance of the coral host. Understanding the balance between the effects of warm and cold winters on disease outbreak will be important in a warming climate. Combining the influence of winter and summer thermal effects resulted in an algorithm that yields both a Seasonal Outlook of disease risk at the conclusion of winter and near real-time monitoring of Outbreak Risk during summer. This satellite-derived system can provide coral reef managers with an assessment of risk three-to-six months in advance of the summer season that can then be refined using near-real-time summer observations. This system can enhance the capacity of managers to prepare for and respond to possible disease outbreaks and focus research efforts to increase understanding of environmental impacts on coral disease in this era of rapidly changing climate. 相似文献
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Cloning and molecular analysis of structural genes involved in flavonoid and stilbene biosynthesis in grape (Vitis vinifera L.) 总被引:23,自引:0,他引:23
Francesca Sparvoli Cathie Martin Attilio Scienza Giuseppe Gavazzi Chiara Tonelli 《Plant molecular biology》1994,24(5):743-755
Genes involved in flavonoid and stilbene biosynthesis were isolated from grape (Vitis vinifera L.). Clones coding for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydoxylase (F3H), dihydroflavonol 4-reductase (DFR), leucoanthocyanidin dioxygenase (LDOX) and UDP glucose:flavonoid 3-O-glucosyl transferase (UFGT), were isolated by screening a cDNA library, obtained from mRNA from seedlings grown in light for 48 h using snapdragon (Antirrhinum majus) and maize heterologous probes. A cDNA clone coding for stilbene synthase (StSy) was isolated by probing the library with a specific oligonucleotide. These clones were sequenced and when the putative products were compared to the published amino acid sequence for corresponding enzymes, the percentages of similarity ranged from 65% (UFGT) to 90% (CHS and PAL). The analysis of the genomic organization and expression of these genes in response to light shows that PAL and StSy genes belong to large multigene families, while the others are present in one to four copies per haploid genome. The steady-state level of mRNAs encoded by the flavonoid biosynthetic genes as determined in young seedlings is coordinately induced by light, except for PAL and StSy, which appear to be constitutively expressed. 相似文献
70.
N J Tikkanen R Dargar B Pfleger B Gonen J M Davie G Schonfeld 《Journal of lipid research》1982,23(7):1032-1038
Monoclonal anti-LDL antibodies were produced in a mouse spleen-myeloma system and purified by affinity chromatography on insolubilized low density lipoprotein (LDL). Five antibodies with different specificities could be distinguished by their immunoreactivities with chemically modified LDL preparations, and by their competition for binding to LDL. One of the antibodies inhibited the binding of (125)I-labeled LDL to the apoB,E receptors of cultured human fibroblasts. The same degree of inhibition was achieved using isolated Fab fragments. This antibody may bind to an antigenic site located near the cellular binding site of LDL-apoB.-Tikkanen, M. J., R. Dargar, B. Pfleger, B. Gonen, J. M. Davie, and G. Schonfeld. Antigenic mapping of human low density lipoprotein with monoclonal antibodies. 相似文献