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br Loss of Chk sensitizes cells to hypoxia
2020-12-17
Loss of Chk 1 sensitizes Hydrocortisone to hypoxia/reoxygenation In contrast to Chk 2, studies have identified Chk 1 as being phosphorylated in an ATR-dependent manner at residue serine 345 during hypoxia [18]. More recently, siRNA mediated inhibition of Chk 1 signaling was found to sensitize ce
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Also important in binding of E
2020-12-17
Also important in binding of E2 to the ER is the hydroxyl on the D ring, which has a stabilizing contact with His-524 in ERα (Fig. 7) and with His-475 in ERβ (Fig. S1) [8,9,36,37]. The spatial relationship of the functional groups on the A and D rings on E2 has been used to develop chemicals contai
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br Membrane receptor Indirect non genomic signaling As menti
2020-12-17
Membrane receptor: Indirect non-genomic signaling As mentioned above, not all CP-673451 australia responses fit the classical genomic model of steroid action. The observation of excessively fast estrogen-induced biological responses led to the development of the hypothesis that estrogen could be
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Recent advances in microarray and next
2020-12-17
Recent advances in microarray [32] and next-generation sequencing [33] based technologies have led to tremendous increases in information about the molecular mechanisms that are responsible for malignant transformation of rare and poorly understood soft tissue sarcomas. However, data interpretation
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ERK and p MAPK signaling pathways play
2020-12-17
ERK and p38 MAPK signaling pathways play critical role in genesis and metastasis of melanoma (Tang et al., 2018). >50% of melanoma N1-Methylpseudouridine sale (Abildgaard and Guldberg, 2015) show abnormal activity of BRAF-RAS-RAF to activate MEK signal that drives the growth-promoting extracellular
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br Thy nephritis is one
2020-12-17
Thy1.1 nephritis is one of the most commonly used models to study the course of immunoglobulin A and other mesangioproliferative nephropathies. To date, most of the studies have focused on mesangial and, to a lesser extent, endothelial cell recovery following capillary damage, whereas data concern
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Several studies have shown that independently of
2020-12-17
Several studies have shown that, independently of body-weight control, the central actions of leptin improve glycemic control in obese diabetic rat and mouse models [62]. For instance, restoration of OB-Rb expression in OB-Rb-deficient mice, and in particular in POMC neurons, was sufficient to norma
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For most enolases fluoride acts
2020-12-17
For most enolases, fluoride acts as an inhibitor, while Mg2+ is the most important metal activator. In yeast systems, metal cations and fluoride bind to enolase at the active center of the enzyme, forming a complex. The complex blocks the binding of substrates to the enzyme in yeast systems, thereb
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At the therapeutic level the logical
2020-12-17
At the therapeutic level, the logical approach to address the cooperation between FGFR4 and EGFR was the combined inhibition of both receptors. To explore the potential efficacy and specificity of this approach, we tested the effect of FGFR and EGFR inhibitors in monotherapy or in combination in syn
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A prominent example of such
2020-12-16
A prominent example of such enzyme is the proteasome, a highly promising target not only in cancer, but also in inflammatory and autoimmune diseases. Circulating proteasomes and respective anti-proteasome autoantibodies were detected in serum samples from patients with autoimmune diseases such as mu
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SIRT is a representative member
2020-12-16
SIRT1 is a representative member of Sirtuins, which is a family of highly conserved NAD+-dependent class III histone deacetylases. SIRT1 deacetylates plentiful nonhistone protein substrates [Atgs, Foxo1, Foxo3, PGC-1α, NF-kB, E2F1 and p53] (Conrad et al., 2016; Gu et al., 2016; Tu et al., 2018) to p
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In addition to cleaving ubiquitins
2020-12-16
In addition to cleaving ubiquitins off modified proteins, DUBs can also cleave between ubiquitin moieties within a polyubiquitin chain to edit the ubiquitin signal. DUBs employ different strategies to recognize polyubiquitin (Figure 1). DUBs that rely only on interactions on the S1 site tend to be R
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Diacylglycerol kinases DGK and are lipid
2020-12-16
Diacylglycerol kinases (DGK) α and ζ are lipid kinases that limit diacylglycerol (DAG)-dependent activation pathways downstream of the TCR (Merida et al., 2015). Their upregulation in tumor infiltrating lymphocytes (TIL) has been linked to generation of hyporesponsive states that contribute to immun
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br Results and discussion br Conclusion A new
2020-12-16
Results and discussion Conclusion A new series of 2-mercapto-quinazolin-4-one analogues is designed and synthesized to possess electron withdrawing or donating functional groups (Cl or CH3O) at position 6- or 7-, 4-methoxyphenyl function at position 3. The 2-mercapto function is used to connec
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An AmDH is engineered by mutating two
2020-12-16
An AmDH is engineered by mutating two conserved amino GSK-LSD1 hydrochloride residues in the active site of an amino acid dehydrogenase (AADH). Starting from the leucine dehydrogenase (LeuDH) from Bacillus stearothermophilus, substituting a serine and leucine at the K68 and N261 positions, respecti
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