Serial number? I am assuming you mean the CD install key. Did you get a copy from a friend or something? Just kidding, but have you made hardware changes? Enough of anything like adding or removing RAM, a HDD, optical drives, ect. Can cause the system to see it as invalid. It's supposed to stop you from activating Windows, but if it's not caught there, it just sees windows as being an illegal copy and blocks downloads.
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