Try regex:
'This iS IIS'.replace(/is/ig, 'as');
Working Example: http://jsfiddle.net/9xAse/
e.g:
Using RegExp object:
var searchMask = "is";
var regEx = new RegExp(searchMask, "ig");
var replaceMask = "as";
var result="This iS IIS".replace(regEx, replaceMask);