Abstract
Cryogenic electron microscopy (cryo-EM) enables molecular imaging of biomolecules at highresolutions in their native-like conditions. Biomolecules are primarily composed of light elements,which can be approximated as weak-phase objects, resulting in nearly no contrast when imaged atfocus. The conventional method introduces a defocus to generate a low-pass filtering-like effectfor the enhancement in the object contrast. However, defocusing leads to phase delocalization andreduces the spatial coherence at high resolutions, producing a fast oscillation in high-frequencyregion and compromising the phase qualities.
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