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For the SAR optimization of the
2019-09-21
For the SAR optimization of the right hand side, it was decided to explore the inclusion of the key carboxylic Voriconazole moiety present in the original DGAT-1 inhibitors from . Analogs were constructed by the synthetic routes outlined in , . In , the methylene-oxy linker was introduced by condens
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The on target in vitro pharmacology of was
2019-09-21
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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br Material and methods br Results
2019-09-21
Material and methods Results Discussion In vitro evidence indicates that LAS191859 is a potent CRTh2 antagonist as demonstrated in GTPγS binding studies with potency in the low nanomolar range and in addition it demonstrates a long receptor residence time. This potency is also maintained in
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Finally unilateral microinjection of CP Astressin B
2019-09-21
Finally, unilateral microinjection of CP-376395, Astressin 2B, CP-376395 + CRF or ASTR 2B + CRF into the BLA (Fig. 3A) or CeA (Fig. 3B) did not significantly alter spontaneous motor activity in the open field test (F4,24 = 0.148, P > 0.05; F4,29 = 0.290, P > 0.05 in the BLA and CeA, respectively, A
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br Effects of estradiol outside the nucleus are often mediat
2019-09-20
Effects of estradiol outside the nucleus are often mediated by classical estrogen receptors Today, it is widely accepted that steroid hormones can signal in ways that do not rely on receptors acting in the nucleus, including activation of receptors localized to the cellular membrane. Rapid effect
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br Regulation of cadherin switching
2019-09-20
Regulation of cadherin switching The downregulation of E-cadherin during cadherin switching is induced by multiple mechanisms, including methylation of the E-cadherin promoter and signaling pathways that activate E-cadherin-suppressing transcription factors [[61], [62], [63]]. During the progress
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br Guidance of B cell localization by EBI br EBI
2019-09-20
Guidance of B cell localization by EBI2 EBI2 expression and B cell disease Although chemoattractant receptors of the GPR family play essential roles in coordinating the migration of lymphocytes for efficient responses against pathogens, their dysregulation can result in the initiation or progr
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Nafamostat Mesylate FOX proteins constitute a large class of
2019-09-20
FOX proteins constitute a large class of transcription factors with multiple functions, from development and organogenesis to regulation of metabolic and immune functions. The Fox transcription factor is characterized by a 100-amino-acid wing helix or forkhead DNA-binding domain. In addition, the FO
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Until recently the first line treatment of RLS
2019-09-20
Until recently, the first line treatment of RLS was the administration of low dose of three dopaminergic drugs, which has been approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of moderate to severe RLS. These compounds are pramipexole (Mirapex), rop
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br Use of recombinant collagen to study
2019-09-20
Use of recombinant collagen to study DDR–collagen interactions Synthetic peptides have proven highly valuable in replicating the characteristics of collagen and in defining the sites on collagen essential for binding and studying protein–collagen interactions. There are, however, disadvantages to
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The field of synthetic cytokine
2019-09-20
The field of synthetic cytokine biology continues to grow through molecular, physiological and pathophysiological insights, as well as via new methodical advances. The approval of chimeric antigen receptor (CAR) T cell immunotherapy by the US Food and Drug administration (FDA) in August 2017 for rel
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During DNA replication p protein binds PCNA in
2019-09-20
During DNA replication p21 protein binds PCNA, in its role as processivity factor, to stop replication when there is DNA damage, and apparently p21 also binds PCNA when this is in complex with Cyc/CDKs [11]. In plants, KRPs (functional analogs of p21), inhibit kinase activity in CycD/CDKs complexes
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Apart from its high affinity the selection of GW as
2019-09-20
Apart from its high affinity, the selection of GW2580 as W-7 hydrochloride lead in our radiotracer development program was motivated by its exceptional selectivity. The observed profound impact of small structural modifications on the selected panel of four kinases tested prompted us to conduct comp
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Recently it was reported that Crm is linked to
2019-09-20
Recently, it was reported that Crm1 is linked to spindle pole body (SPB) by Spc72 in 7-Nitroindazole kinase yeast [9]. Spc72 and Spc110 are two specific receptors of γ-tubulin complex (Tub4), which target Tub4 to SPB and mediate the nucleation of microtubules from SPB [20]. It was found that disrup
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Introduction Formate dehydrogenase enzymes FDHs are a group
2019-09-19
Introduction Formate dehydrogenase enzymes (FDHs) are a group of heterogeneous proteins that catalyse the reversible formate () oxidation to carbon dioxide () (Eq. (1)). These enzymes are classified in two families, one gathering the enzymes that hold no redox-active centres and another that includ
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