From here:
http://acepilots.com/planes/b17.html
As the heavy bomber demands of the North African campaign eased in the winter of 1942-43, the air war in Northwest Europe accelerated. On January 27, 1943, for the first time, American bombers hit inside of Germany itself, the submarine facilities at Wilhelmshaven.
A turning point was reached on April 17, when 115 Flying Fortresses bombed the Focke-Wulfe factory in Bremen. As if defending its nest, the Luftwaffe struck hard, knocking down sixteen B-17's (a 15 percent loss rate - on a single mission!). Soon, ten-to-fifteen percent losses became the norm, as the Luftwaffe improved their tactics, in particular by attacking the B-17's head on. Thus the famous phrase "Bandits at twelve o'clock high!"
But the Eighth continued grimly on, throughout 1943, next targeting ball-bearing production, considered a vital weak point in aviation manufacturing. On the 17th of August, a large force of 376 bombers raided Schweinfurt and Regensburg. Sixty bombers, with six hundred aircrew, didn't come back. 16 percent losses. At that rate, the Eighth Air Force could not continue. When B-17G's began to arrive in August and September, the forward machine guns in their chin turrets helped a little. The appalling wastage continued:
September 6 - Over 400 bombers attacked the Stuttgart ball-bearing plant; 45 were lost.
October 14 - Schweinfurt again. 291 B-17's went out; 60 went down.
January 11, 1944 - German aircraft industry targets. 600 Flying Fortresses were sent out. Because of bad weather, only 238 reached Germany; 60 were shot down.