全文获取类型
收费全文 | 86篇 |
免费 | 6篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 4篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 6篇 |
2013年 | 6篇 |
2012年 | 9篇 |
2011年 | 1篇 |
2010年 | 3篇 |
2009年 | 2篇 |
2008年 | 5篇 |
2007年 | 2篇 |
2006年 | 3篇 |
2004年 | 3篇 |
2003年 | 5篇 |
2002年 | 1篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有92条查询结果,搜索用时 15 毫秒
61.
62.
Letizia Albarran Sergio Regodón Gines M. Salido Juan A. Rosado 《Channels (Austin, Tex.)》2017,11(1):84-88
The store-operated Ca2+ entry-associated regulatory factor (SARAF), a protein expressed both in the endoplasmic reticulum and the plasma membrane, has been presented as a STIM1-interacting protein with the ability to modulate intracellular Ca2+ homeostasis. SARAF negatively modulates store-operated Ca2+ entry (SOCE) by preventing STIM1 spontaneous activation and regulating STIM1-Orai1 complex formation. In addition, SARAF is a negative regulator of Ca2+ entry through the arachidonate-regulated Ca2+ (ARC) channels. Here we explored the possible role of the surface expression of SARAF on the location of STIM1 in the plasma membrane. In NG115-401L cells, lacking a detectable expression of native STIM1, transfection with pHluorin-STIM1, which is able to translocate to the cell surface, enhances the plasma membrane location of SARAF as compared to cells transfected with YFP-STIM1, lacking the ability to translocate to the cell surface. These findings suggest that the surface location of SARAF is dependent on the expression of STIM1 in the plasma membrane. 相似文献
63.
Antonio Gutiérrez Leyre Bento Antonia Maria Bautista-Gili Francesc Garcia Jordi Martinez-Serra Blanca Sanchez Clara Martorell Jordi Gines Lucia Garcia Eva Gimeno Mariana Ferraro Raquel Del Campo Joan Bargay Albert Perez Javier Vercher Miguel Scaff Ana Pacheco Carmen Ballester Florencia Garcia Rafael Ramos Antonio Salar Joan Besalduch 《PloS one》2015,10(4)
DLBCL is an aggressive lymphoma treated with R-CHOP. Recently, attempts have been made to improve the outcome by increasing both dose-density and intensity but there have been no benefits in terms of survival. When treating malignancies RDI is important to consider but there is little published information on DLBCL. The purpose of this study was to analyze the differential prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14. From January 2001 to August 2013 we included DLBCL patients homogenously treated with R-CHOP21 or R-CHOP14, with or without radiotherapy, at University Hospital Son Espases, Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona (N = 157). In order to avoid selection bias the patients were retrospectively identified from the Pathology Department and Pharmacy registries. Median follow-up was 68 months. There was no difference in the response or survival between the two cohorts. In the R-CHOP21 group, both a reduction higher than 15% in RDI (RR 7.41) and R-IPI (RR 2.99) were independently associated with OS. However, a reduction higher than 15% in RDI (RR 4.41) was only noted for PFS. In the R-CHOP14 group, NCCN-IPI (RR 7.09) and B-symptoms (RR 5.37) for OS; AA stage III-IV (RR 6.26) and bulky disease (RR 4.05) for PFS. There was a trend towards a higher rate of RDI reduction observed in the R-CHOP14 group but it only made an impact in the R-CHOP21 group. We conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival, but only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions. 相似文献
64.
Marta Palomo Manel Vera Susana Martin Sergi Torramad‐Moix Julia Martinez‐Sanchez Ana Belen Moreno Enric Carreras Gins Escolar Aleix Cases Maribel Díaz‐Ricart 《Journal of cellular and molecular medicine》2020,24(2):1713-1723
Endothelial dysfunction is an earlier contributor to the development of atherosclerosis in chronic kidney disease (CKD), in which the role of epigenetic triggers cannot be ruled out. Endothelial protective strategies, such as defibrotide (DF), may be useful in this scenario. We evaluated changes induced by CKD on endothelial cell proteome and explored the effect of DF and the mechanisms involved. Human umbilical cord vein endothelial cells were exposed to sera from healthy donors (n = 20) and patients with end‐stage renal disease on haemodialysis (n = 20). Differential protein expression was investigated by using a proteomic approach, Western blot and immunofluorescence. HDAC1 and HDAC2 overexpression was detected. Increased HDAC1 expression occurred at both cytoplasm and nucleus. These effects were dose‐dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up‐regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule‐1, surface Toll‐like receptor‐4, von Willebrand Factor and reactive oxygen species. Moreover, DF down‐regulated HDACs expression through the PI3/AKT signalling pathway. HDACs appear as key modulators of the CKD‐induced endothelial dysfunction as specific blockade by trichostatin A or by DF prevents endothelial dysfunction responses to the CKD insult. Moreover, DF exerts its endothelial protective effect by inhibiting HDAC up‐regulation likely through PI3K/AKT. 相似文献
65.
Berna-Erro A Galan C Dionisio N Gomez LJ Salido GM Rosado JA 《Biochimica et biophysica acta》2012,1823(8):1242-1251
Discharge of the intracellular Ca(2+) stores activates Ca(2+) entry through store-operated channels (SOCs). Since the recent identification of STIM1 and STIM2, as well as the Orai1 homologs, Orai2 and Orai3, the protein complexes involved in Ca(2+) signaling needs re-evaluation in native cells. Using real time PCR combined with Western blotting we have found the expression of the three Orai isoforms, STIM1, STIM2 and different TRPCs in human platelets. Depletion of the intracellular Ca(2+) stores with thapsigargin, independently of changes in cytosolic Ca(2+) concentration, enhanced the formation of a signaling complex involving STIM1, STIM2, Orai1, Orai2 and TRPC1. Furthermore, platelet treatment with the dyacylglicerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) resulted in specific association of Orai3 with TRPC3. Treatment of platelets with arachidonic acid enhanced the association between Orai1 and Orai3 in human platelets and overexpression of Orai1 and Orai3 in HEK293 cells increased arachidonic acid-induced Ca(2+) entry. These results indicate that Ca(2+) store depletion results in the formation of exclusive signaling complexes involving STIM proteins, as well as Orai1, Orai2 and TRPC1, but not Orai3, which seems to be involved in non-capacitative Ca(2+) influx in human platelets. 相似文献
66.
Alfredo D. Guerron Rashmi Rawat Arpana Sali Christopher F. Spurney Emidio Pistilli Hee-Jae Cha Gouri S. Pandey Ramkishore Gernapudi Dwight Francia Viken Farajian Diana M. Escolar Laura Bossi Magali Becker Patricia Zerr Sabine de la Porte Heather Gordish-Dressman Terence Partridge Eric P. Hoffman Kanneboyina Nagaraju 《PloS one》2010,5(6)
Background
The number of promising therapeutic interventions for Duchenne Muscular Dystrophy (DMD) is increasing rapidly. One of the proposed strategies is to use drugs that are known to act by multiple different mechanisms including inducing of homologous fetal form of adult genes, for example utrophin in place of dystrophin.Methodology/Principal Findings
In this study, we have treated mdx mice with arginine butyrate, prednisone, or a combination of arginine butyrate and prednisone for 6 months, beginning at 3 months of age, and have comprehensively evaluated the functional, biochemical, histological, and molecular effects of the treatments in this DMD model. Arginine butyrate treatment improved grip strength and decreased fibrosis in the gastrocnemius muscle, but did not produce significant improvement in muscle and cardiac histology, heart function, behavioral measurements, or serum creatine kinase levels. In contrast, 6 months of chronic continuous prednisone treatment resulted in deterioration in functional, histological, and biochemical measures. Arginine butyrate-treated mice gene expression profiling experiments revealed that several genes that control cell proliferation, growth and differentiation are differentially expressed consistent with its histone deacetylase inhibitory activity when compared to control (saline-treated) mdx mice. Prednisone and combination treated groups showed alterations in the expression of genes that control fibrosis, inflammation, myogenesis and atrophy.Conclusions/Significance
These data indicate that 6 months treatment with arginine butyrate can produce modest beneficial effects on dystrophic pathology in mdx mice by reducing fibrosis and promoting muscle function while chronic continuous treatment with prednisone showed deleterious effects to skeletal and cardiac muscle. Our results clearly indicate the usefulness of multiple assays systems to monitor both beneficial and toxic effects of drugs with broad range of in vivo activity. 相似文献67.
Vasily A Shenshin Camille Lescanne Guillaume Gines Yannick Rondelez 《Nucleic acids research》2021,49(13):7765
In vitro molecular circuits, based on DNA-programmable chemistries, can perform an increasing range of high-level functions, such as molecular level computation, image or chemical pattern recognition and pattern generation. Most reported demonstrations, however, can only accept nucleic acids as input signals. Real-world applications of these programmable chemistries critically depend on strategies to interface them with a variety of non-DNA inputs, in particular small biologically relevant chemicals. We introduce here a general strategy to interface DNA-based circuits with non-DNA signals, based on input-translating modules. These translating modules contain a DNA response part and an allosteric protein sensing part, and use a simple design that renders them fully tunable and modular. They can be repurposed to either transmit or invert the response associated with the presence of a given input. By combining these translating-modules with robust and leak-free amplification motifs, we build sensing circuits that provide a fluorescent quantitative time-response to the concentration of their small-molecule input, with good specificity and sensitivity. The programmability of the DNA layer can be leveraged to perform DNA based signal processing operations, which we demonstrate here with logical inversion, signal modulation and a classification task on two inputs. The DNA circuits are also compatible with standard biochemical conditions, and we show the one-pot detection of an enzyme through its native metabolic activity. We anticipate that this sensitive small-molecule-to-DNA conversion strategy will play a critical role in the future applications of molecular-level circuitry. 相似文献
68.
Development of a simple embedding procedure allowing immunocytochemical localization at the ultrastructural level 总被引:1,自引:0,他引:1
G Escolar J J Sauk M L Bravo M Krumwiede J G White 《The journal of histochemistry and cytochemistry》1988,36(12):1579-1582
Immunobed solution A is a water-soluble acrylic compound recently developed for immunocytochemical localization at the light microscopic level. In this study, we combined it with methyl methacrylate (MMA) to achieve sufficient hardness to obtain ultra-thin sections. Samples of platelets were dehydrated and embedded in the water-soluble acrylic mixture (WSAM). The embedding process was carried out at 4 degrees C and final polymerization was induced with either chemical (benzoyl peroxide) or physical (UV light) catalysts. Tubulin was localized at the ultrastructural level in sections embedded according to these two methods. Results were compared with those obtained in platelets processed in Lowicryl. Dehydration and embedding with the WSAM yielded a preservation of antigenicity similar to that obtained in Lowicryl. The new procedure benefits from the low temperature achieved during polymerization, providing good ultrastructural morphology and immunolocalization of protein antigens with the simplicity of a routine embedding procedure for light microscopy. 相似文献
69.
Summary We estimate the number of blastoderm cells which generate the thoracic imaginal discs ofDrosophila. At hatching the wing disc is twice the size of the haltere disc, but the results suggest that both discs develop from a similar number of blastoderm cells. Two homeotic mutations, which transform the haltere into wing, affect embryonic growth but not the primordial number. All the segmental primordia may be of similar size and each may be similarly subdivided into a larger anterior, and a smaller posterior polyclone. 相似文献
70.
Diego A. Golombek Esteban Escolar Leila J. Burin Marí a G. De Brito S nchez Diego Fern ndez Duque Daniel P. Cardinali 《Chronobiology international》1992,9(2):124-131
We endeavored to determine whether three behavioral effects of melatonin in rodents, i.e., depression of locomotor activity in hamsters, analgesia in mice, and impairment of 3-mercaptopropionic acid (3-MP) convulsions, exhibited the time dependency known to occur for several neuroendocrine effects of the hormone. Activity was monitored and registered by means of an optical acto-meter, and analgesia was assessed by the hot-plate procedure. Locomotor activity, analgesia, and seizure susceptibility were maximal at the beginning of the scoto-phase and minimal at noon. The effects of melatonin on the three parameters peaked at early night. The administration of the benzodiazepine antagonist fluma-zenil, although unable by itself to modify locomotor activity, pain, or seizure threshold, blunted the activity of melatonin. These results suggest that the time-dependent effects of melatonin on specific rodent behaviors may be mediated by central synapses employing 7-aminobutyric acid (GABA) as an inhibitory transmitter. 相似文献