We study the nuclear parton distribution functions on the basis of our recently developed semi-microscopic model, which takes into account a number of nuclear effects including nuclear shadowing, Fermi motion and nuclear binding, nuclear meson-exchange currents, and off-shell corrections to bound nucleon distributions. We discuss in detail the dependencies of nuclear effects on the type of parton distribution (nuclear sea vs valence), as well as on the parton flavor (isospin). We apply the resulting nuclear parton distributions to calculate ratios of cross sections for proton-induced Drell-Yan production off different nuclear targets. We obtain a good agreement on the magnitude, target and projectile $x$, and the dimuon mass dependence of proton-nucleus Drell-Yan process data from the E772 and E866 experiments at Fermilab. We also provide nuclear corrections for the Drell-Yan data from the E605 experiment.
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