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Then what is the solution to tackle
2021-02-25
Then what is the solution to tackle DNA damage-induced metabolic decline? The culprit here may be not DNA damage signaling per se, but rather the persistent activation of the DNA damage signaling pathways due to age-related accumulation of DNA damage. DNA repair, including repair by NHEJ, is an esse
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br Materials and methods br Results br Discussion CDK
2021-02-24
Materials and methods Results Discussion CDK4 has been identified recently as a potential therapeutic target in human breast cancer, liposarcoma, melanoma, and glioblastoma [[37], [38], [39]]. Due to the importance of CDK4 activity in cancer cells, CDK4 inhibitors have emerged as promising
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br Acknowledgements We are grateful to
2021-02-24
Acknowledgements We are grateful to the National Natural Science Foundation of China (Grant Nos. 21571033 and 81503099) and the New Drug Creation Project of the National Science and Technology Major Foundation of China (Grant No. 2015ZX09101032) for financial aids to this work. The research was a
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In the present study we determined concentration response re
2021-02-24
In the present study, we determined concentration–response relationships for selected synthetic progestogens using in vitro luciferase transactivation assays driven by PR, ARα and ARβ from Murray–Darling rainbowfish () and compared the profiles with those obtained from similar assays based on human
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In contrast irinotecan has shown much less myelosuppression
2021-02-24
In contrast, irinotecan has shown much less myelosuppression and may be more active in Ewing sarcoma both alone and in combination with temozolamide. One phase II study of 13 heavily pretreated Ewing sarcoma patients demonstrated a response rate of 38% including 2 complete responses (Bisogno et al.,
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Further modifications on the position of compound
2021-02-24
Further modifications on the 8-position of compound led to compound 4 (8-pCPT-2′--Me-cAMP, a.k.a. 007, ), which is a potent (half-maximal activation of EPAC1 at 2.2µM) and selective (about 100-fold EPAC/PKA selectivity) EPAC agonist. Since the discovery of compound , it has been widely used as a po
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br Molecular characterization of LEI L
2021-02-24
Molecular characterization of LEI/L-DNase II LEI, like most serpins, is a metastable protein and its anti-protease activity is related to its “stressed to relaxed transition”. So that, the inhibition of elastase by the well described suicide mechanism generates the cleaved form of LEI (see Padron
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In vitro studies in NSCLC
2021-02-24
In vitro studies in NSCLC cell lines expressing EGFR mutants (T790M mutation, exon 19 deletion E746-A750, L858R/T790M double mutation), demonstrated that Rociletinib potently inhibits proliferation in the mutant EGFR NSCLC GM6001 with Growth inhibition (GI50) values ranging from 7 to 32 nmol/L. In
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Why are Tfh cell dynamics so fundamentally different in
2021-02-24
Why are Tfh cell dynamics so fundamentally different in naive and immune animals? Initially, GC Nilvadipine must pass stringent affinity and specificity checkpoints to ensure only high-affinity non-self-reactive cells are selected. Therefore, restricting primary Tfh cells with the greatest helper c
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In addition to playing important roles in the
2021-02-24
In addition to playing important roles in the immune system, EBI2 is also expressed in the rucaparib of the central nervous system (CNS), namely astrocytes, and this receptor regulates astrocyte signalling, as well as astrocyte cell migration (Rutkowska et al., 2015, Rutkowska et al., 2016a). Moreo
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The homologous DDRs are composed
2021-02-23
The homologous DDRs are composed of an N-terminal discoidin homology domain, followed by a sequence of ∼220 amino acids unique to the DDRs, a transmembrane domain, a large juxtamembrane domain, and a conserved cytoplasmic tyrosine kinase domain. In a previous study, we demonstrated that DDR activati
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br Material and methods br Results br Discussion Monomeric
2021-02-23
Material and methods Results Discussion Monomeric CDK5 shows no enzymatic activity and requires the association with a regulatory partner for activation (Dhavan and Tsai, 2001). Here, we found that CDK7 might be one of the partners required for activation of CDK5 in the skin tissue, based o
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Compound was generated using a literature procedure and
2021-02-23
Compound was generated using a literature procedure and required two-step Dess–Martin-periodinane/Pinnick oxidation prior to the methylation of the sulfonamide. Compound () was obtained from the Suzuki coupling of the methyl ester intermediate (en route to Ropivacaine HCl synthesis ). Hydrolysis
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In addition to carbamates organophosphates are classic
2021-02-23
In addition to carbamates, organophosphates are classic inhibitors of cholinesterases. Previous studies with aquatic organisms have demonstrated their sensitivity to such chemicals. For example, individuals of the freshwater fish Colossoma macropomum exposed to the organophosphate dichlorvos, chlorp
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Increasing age among middle aged
2021-02-23
Increasing age among middle-aged subjects (30–59years old) was associated with higher levels of cholesterol synthesis markers (although without statistical significance) and also of cholesterol Aprepitant markers (with statistical significance for campesterol and sitosterol); this finding is consis
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