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Frank Gore didn’t waste time. As soon as he saw his quarterback sit down in front of his locker following a 26-3 home defeat to the defending Super Bowl champion New York Giants, the 49ers all-time leading rusher immediately went over to give words of encouragement to Alex Smith.

The words couldn’t be heard, but Gore’s upbeat body language spoke volumes.

Following the team’s first home loss of the season with the largest margin of defeat in Jim Harbaugh’s 22 regular season games with the San Francisco 49ers, two of the longest tenured offensive players had each other’s backs after a difficult defeat.

“We beat ourselves on a lot of stuff out there,” said Gore, one of the offensive co-captains along with Smith. “We didn’t play San Francisco football today. They came in and got a win.”

Smith completed 19 of 30 passes for 200 yards and threw three interceptions on a day where he was constantly pressured by New York’s relentless defensive line. The 49ers quarterback entered the Week 6 matchup with the highest quarterback rating in the NFL and finished Sunday’s one-sided game against the Giants with a 43.1 rating.

Smith and backup quarterback Colin Kaepernick were sacked a combined six times on Sunday.

“They’re a good defense,” Smith said. “They don’t give up anything easy and we forced some things tonight. I felt like I forced some things, uncharacteristic, I turned the ball over. Any time you turn the ball over like that, it’s tough to win.”

Gore, himself, was held in check. The dangerous rusher finished the game with a season-low eight carries for 36 yards.  The 49ers entered Sunday averaging 196.2 rushing yards per game, best in the NFL, but left Sunday’s NFC title game rematch with 80 yards on 17 carries.

While looking for consecutive wins over all three New York teams in consecutive weeks for the first time in franchise history, the 49ers learned just how talented the defending Super Bowl champs can be on the big stage.

“We didn’t do enough,” Harbaugh said. “We put ourselves in a position we couldn’t come back from, more turnovers than we’re accustomed to. Plan-wise, it wasn’t the right one. We’ll try to figure out what the next one we’ll be.”

The 49ers picked up seven of their 14 first downs in the first quarter alone, but couldn’t capitalize on the early momentum. San Francisco seized a 3-0 lead, but also saw David Akers miss two first-half field goals while getting down 10-3 to the Giants at halftime.

The uncharacteristic offensive play, penalties and turnovers, began for the 49ers in the second quarter.

Smith was first intercepted by New York cornerback Prince Amukamara on a deep sideline route intended for tight end Delanie Walker.

The 49ers quarterback said his injured middle finger on his throwing hand didn’t cause the takeaways.

“All different,” Smith said of the interceptions.

The Giants capitalized immediately on Smith’s second interception of the season. New York’s two-time Super Bowl winning quarterback Eli Manning threw a 39-yard deep ball to Domenik Hixon down the right sideline and into 49ers territory. Hixon later converted another New York first down with a 16-yard first down.

Those catches were key.

On the next play, Manning completed a 6-yard touchdown pass to Victor Cruz to cap a 7-play, 67-yard scoring drive. It was also the first touchdown allowed by San Francisco’s defense in nine quarters.

“It’s pretty tough,” safety Donte Whitner said after the one-sided outcome. “We didn’t get any turnovers on defense to help our offense out.”

Besides failing to record a turnover, San Francisco did not sack Manning on the day while allowing him to complete 15 of 28 passes for 193 yards and one touchdown.

Later in the second quarter, Manning had his streak of nine consecutive completions snapped on New York’s final drive of the first half. It appeared as though the 49ers gained momentum thanks to cornerback Tarell Brown blocking a 40-yard field goal attempt by Lawrence Tynes.

The momentum, however, was short-lived. Even with Kaepernick completing a 36-yard pass to former New York Giants wideout Mario Manningham (who led the 49ers with five catches for 72 yards against his former teammates), Akers missed a 52-yard attempt at the end of the first half.

Special teams remained a focal point in the third quarter. New York rookie running back David Wilson supplied a 66-yard kickoff return to open the second half.

The big return eventually helped set up Ahmad Bradshaw’s 1-yard rushing touchdown to cap a back-breaking, 7-play, 32-yard scoring drive that put New York up by 14 points.

With the game at 17-3, the 49ers allowed their first rushing touchdown in 14 games.

Bradshaw finished with the day with 27 carries for 116 yards – making him first opponent to rush for more than 100 yards against the 49ers all season.

“I felt our defense was in bad situations,” Harbaugh said. “Not our best game.”

In response to Bradshaw’s touchdown, Smith threw his second interception of the game when his slant pass intended for Manningham sailed high into the arms of Giants safety Antrel Rolle.  

Rolle jumped another route in the third quarter which set up a 22-yard Tynes field goal. In total, the Giants kicker connected on four field goals on the day with his last being a 32-yard attempt for the game’s only points in the fourth quarter.

It also marked the end of New York’s 26 unanswered points following Akers’ 42-yard make.

“Tough loss for us,” Harbaugh said after his team moved to 4-2. “I told the guys we need to bounce back fast.”

San Francisco will have the Seattle Seahawks in town this Thursday night for a nationally televised NFC West matchup on NFL Network’s “Thursday Night Football.”

Besides marking the team’s first divisional game of 2012, it’ll be a game with first-place implications on the line. Seattle, San Francisco and the Arizona Cardinals are now tied atop the division.

“We have to bounce back, we have to,” tight end Vernon Davis said. “We don’t have time to play around. We have to go to practice and get ready for the next one.”