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br Conclusion Our study demonstrates that the
2020-04-13
Conclusion Our study demonstrates that the effects of Epac activation are strongly conditioned by the steady-state Ca levels at which the myocyte is functioning. As intracellular Ca increases, the activity of CaMKII enhances and the phosphorylation of its SR substrates acquires different relevanc
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Triciribine synthesis In the present study promoting
2020-04-13
In the present study, promoting bile Triciribine synthesis synthesis by activating EP4 receptors was shown to exert protection against hepatic steatosis. This finding may be relevant for treatment of non-alcoholic fatty liver disease, a major cause of liver disease and prominent indication for live
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In addition to providing substantial insight into substrate
2020-04-13
In addition to providing substantial insight into substrate recognition, structural studies have revealed important details about mechanisms of glycosylation and HCF-1 cleavage [28,30,33]. Activation of the nucleotide-sugar is accomplished through interactions of the β-phosphate with the N-terminus
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Introduction CYP is a superfamily of heme containing monooxy
2020-04-13
Introduction CYP450 is a superfamily of heme-containing monooxygenases, many of which are expressed in the liver, and they are significant phase-I MYK-461 receptor in drug metabolism and detoxification. There are three subfamilies (CYP1, CYP2 and CYP3) that are mainly involved in the metabolism of
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br Introduction Detection of driver
2020-04-13
Introduction Detection of driver mutations in patients with advanced non-small cell lung cancer (NSCLC) is critical because they receive great benefit from kinase inhibitors [[1], [2], [3], [4]]. However, it is often difficult to obtain tumor tissue in advanced NSCLC patients. Cell-free DNA (cfDN
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The discoidin domain receptors DDR and DDR are receptor tyro
2020-04-10
The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases (RTKs) that are stimulated by collagen in the extracellular matrix (ECM). Unlike most other RTKs, they form ligand-independent stable dimers that are non-covalently linked. This ECM activation induces receptor phosphorylati
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KPT-185 br Results br Discussion Taking advantage of the hig
2020-04-10
Results Discussion Taking advantage of the highly specific protein–protein interactions among cognate KPT-185 that mediate SUMO conjugation to substrates, we have developed a novel strategy for achieving inhibition of SUMO conjugation in vivo based on disruption of SUMO E1–E2 interactions. We
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E cadherin is an adhesive
2020-04-10
E-cadherin is an adhesive Ca2+ dependent transmembrane protein mediating tight and strong cell-cell adhesion through homophilic interactions. There is strong evidence in favour of the major role of E-cadherin in melanocytes adhesion to keratinocytes in the clemastine (Tang et al., 1994). The expres
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Using characteristic features of ECM proteins and a
2020-04-10
Using characteristic features of ECM proteins and a computational pipeline combining interrogation of protein and gene databases, we previously defined the matrisome as the ensemble of ECM and ECM-associated proteins [[16], [17], [18]]. In mammals, the matrisome represents 4% of the genome, or appro
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br Iterative design approach overview An iterative design
2020-04-10
Iterative design approach overview An iterative design strategy is used to identify a peptidase-resistant reporter that acts as an efficient substrate for kinases in cell lysates as well as intact cells (Fig. 1). In this process, small-scale, rationally designed libraries are used to screen pepti
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br Introduction Mammalian proteases comprise both the peptid
2020-04-10
Introduction Mammalian proteases comprise both the peptidases or exopeptidases, which act at the N- or C-terminal positions of polypeptides, and proteinases or endopeptidases, which are capable of cleaving peptide bonds in the central regions of polypeptides. The endopeptidases are classified in
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Previously we have shown that the overexpression of
2020-04-10
Previously, we have shown that the overexpression of ERRγ induces exercise-like oxidative muscle remodeling without engaging changes in the expression level or activity of PGC1α (Narkar et al., 2011). In this study, overexpression of ERRγ in PKO muscle reveals that ERRγ-activated target genes can ac
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The on target in vitro pharmacology of was then
2020-04-10
The on target in vitro pharmacology of 18 was then further explored, first in respect of murine CRTh2 receptor activity (Table 5), where similar levels of activity were found in both a binding and functional assay compared with the human orthologue, consistent with our earlier observations in the su
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Current therapeutic protocols in OS and ES consist
2020-04-10
Current therapeutic protocols in OS and ES consist of neoadjuvant chemotherapy and local surgical resection, followed by adjuvant chemotherapy. These treatments lead to a 70% overall survival for localized disease but can decrease to 15% in case of metastasis. With CS being resistant to conventional
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br Results and discussion br Conclusions In conclusion
2020-04-10
Results and discussion Conclusions In conclusion, we have developed rational strategies that allowed us to successfully identify a series of novel analogs structurally related to to modulate the activity of estrogen-related receptors (ERRγ and ERRβ), which are constitutively active. All of th
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