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  • Cellular Neonatal Fc Receptor Recycling Efficiencies can Differentiate . . .
    Our results demonstrate that the interplay of non-specific endocytosis rates, pH-dependent non-specific interactions, and engagement with FcRn all contribute to the overall recycling efficiency of therapeutic monoclonal antibodies
  • The Internalization and Intracellular Trafficking of ADCs
    As ADC internalizes, it is transported to lysosome for degradation and payload is released to target intracellular compartments to exert the anti-cancer effect
  • ADCs may pass through vascular endothelium by FcRn-mediated. . .
    Antibody-drug conjugates (ADCs) are ushering in the next era of targeted therapy against cancer An ADC for cancer therapy consists of a potent cytotoxic payload that is attached to a
  • Severing Ties: Quantifying the Payload Release from Antibody Drug . . .
    Non-cleavable linkers will only release their payload upon delivery to the lysosomal compartment and subsequent antibody degradation The catabolite of this process is the payload-linker-amino acid, which cannot readily pass through membranes
  • Uptake and Potential Toxicity Mechanism of Non-Target-Dependent ADC—III . . .
    In each endocytosis cycle, only ADC that is not bound to FcRn is transported to lysosomes for catabolism and payload release From a safety point of view, FcRn binding is also important for reducing the accumulation and catabolism of ADC in normal cells to release cytotoxic payloads
  • FcRn mediates fast recycling of endocytosed albumin and IgG from early . . .
    Here, we have analysed the recycling of albumin and IgG in primary mouse macrophages expressing the human FcRn, and have identified a novel fast recycling pathway from early macropinosomes that protects these ligands from degradation
  • Antibody Internalization | Thermo Fisher Scientific - US
    When antibodies bind to cell-surface receptors, they trigger endocytosis, internalizing the receptors and antibodies into the cell This process is vital in research of targeted drug delivery to cancer cells, especially with antibody-drug conjugates (ADCs)
  • Fundamental properties and principal areas of focus in antibody–drug . . .
    The assessment of ADC developability requires comprehensive evaluation of both antibody-related characteristics (including structural homogeneity, thermal stability, solubility, and target specificity) and linker-payload physicochemical properties
  • Cellular Neonatal Fc Receptor Recycling Efficiencies can Differentiate . . .
    Single parameter in vitro assessments to predict mAb in vivo behavior have oftentimes failed to directly correlate with mAb CLind This may be due to their inability to fully recapitulate the biological dynamics important for mAb disposition or because they only focus on a single aspect, such as on-chip hFcRn-hIgG binding studies 54 A key advantage to the use of a cellular hFcRn recycling assay is its integration of multiple processes important for the dis-position of mAbs 34,47-50,54 Our results agree with the capabilities demonstrated by other cell-based assessments of IgG-FcRn for mAb CLind while further emphasizing the multifaceted relationship between cellular uptake and FcRn-mediated recycling 34,35,47-50 Cell-based systems offer their readouts within a biological frame-work, which has been directly shown as advantageous for studying FcRn-IgG and FcRn-Fc interactions compared to standard biophysical approaches 51,55 Subsequently, physiologically based PK models will play a crucial role for the extension of in vitro results to the patient by helping to describe the net impact of in vitro behaviors on mAb disposition 86,87 Combinatorial methodologies that utilize known drug-like attributes for mAbs will be critically needed to develop successful Fc-based half-life extension strategies as the biopharmaceutical industry transitions to more complex structures for their biologic pipelines 88-92
  • The therapeutic age of the neonatal Fc receptor - Nature
    FcRn binds to the Fc portion of IgGs in a pH-dependent manner and protects them from intracellular degradation It also allows their transport across polarized cells that separate tissue





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