You can mark a period as unavailable by going to Site Settings > Resource Vacations. Here, you can define either one-time or recurring periods when your resources are unavailable. You can also access this page directly via this link.
If you want to mark many specific dates as unavailable or partly available, you should do this on the Availability page. This page allows you to view and set availability for each day of the year on a calendar—or for each time unit if your resources are hour-based.
Another way to add vacations is on the Schedule page, where you can do this visually by clicking and dragging across the desired period, then clicking on block period.
Please note that if you already have existing reservations for a period you're marking as unavailable, the system will inform you about this and mark them as conflicts. See this question for more info.