Lets see, well disease, poor living conditions, and genetic mutations.
Answer - It will allow the molecules move against the concentration gradient which is pretty much acting against it. (Low concentration gradient TO high concentration)
Reason - It will use energy. For example in a river theres a down flow but if you want to get up top of the river you must go against it by going against the current. Pretty much the same thing but its happening with the cell in a active mode.
Amphibian means two-lives, Frogs began there lives in the water as eggs and then grow to tadpoles, when they are fully developed they live on land.