Yes, this is possible using a free utility called Handle, by Mark Russinovich.
It can be download here from Microsoft.
This runs from the command line, and will tell you which program has a particular file or directory open, based on whether it has an open handle to that resource.
By running handle.exe with the -c flag, you can also force the specified handle closed, which will unlock the resource. But fair warning: this will likely cause the application using the resource to crash, perhaps even the entire system to become unstable. So I wouldn't make a habit of doing this; only use it for special cases like debugging where you expect some instability.
