Syrian warplanes bombed the nation’s largest city Tuesday, activists said, a dramatic escalation in the 16-month uprising and a stark sign of the government’s growing desperation as it tries to reverse the recent momentum of rebel forces.

Aleppo, like Damascus, the Syrian capital, had long been seen as a stronghold of support for President Bashar al-Assad. But the unrest has spread to the city, Syria’s commercial capital, in recent days, adding to a sense that the regime is losing control after the assassinations last week of four of its top security officials in a bombing.

Tuesday’s aerial bombing of Aleppo, the first of its kind in the conflict, was part of a coordinated assault by government forces that included heavy artillery shelling and rockets launched from military helicopters. The attacks targeted Tariq Bab, a residential area east of Aleppo, as well as the neighborhoods of Sakhour and Masaken Hanano in Aleppo, according to the Local Coordination Committees, an activist network.

Although helicopter gunships have been used in the past, the government’s decision to deploy fixed-wing aircraft appeared to be an effort to intimidate the rebel forces by signaling that the regime had yet to use its full military arsenal. Syria has one of the largest air forces in the Middle East, and its use in battling the rebels could give the government a critical advantage over a rebel force that has struggled to acquire heavy weapons.

Meanwhile, Syria’s northern neighbor, Turkey, announced Wednesday morning that it will close all the border gates to truck traffic between the two countries, effectively blocking vital supply routes into Syria, but keeping them open for refugees. Last week, Syrian rebels seized control of several border gates through which thousands of refugees have been crossing into Turkey.

In Washington, Secretary of State Hillary Rodham Clinton said that despite Tuesday’s massive assault, rebel fighters have been gaining control of swaths of territory and are establishing “a safe haven” within the country. She also called on the opposition to begin working on “interim governing entities” and to pledge to protect the rights of all Syrians.

Clinton urged the Syrian rebels to safeguard the regime’s chemical and biological weapons. After recent reports that the government has been moving its vast stockpiles of sarin, mustard gas and VX nerve gas, there has been growing speculation that the military might use chemical weapons against the rebels. During a news conference Monday, Foreign Ministry spokesman Jihad Makdissi said the Syrian military’s stocks of chemical and biological weapons would be used only against external enemies.

A BBC reporter who was on the outskirts of Aleppo at the time of Tuesday’s assault reported seeing what appeared to be Russian-made MiG fighter jets streaking across the sky. “We watched as they dropped in, bombing and strafing rebel positions,” Ian Pannell wrote in an online account of the attack. “Dead and wounded civilians and fighters were taken to hospitals and makeshift clinics as the human cost of this conflict continues to grow.”

Fighters from the Free Syrian Army had spread out in at least six neighborhoods by Tuesday evening, setting up checkpoints and digging in, according to an activist in Aleppo who uses the name Mohammed Halabi. There was also heavy fighting in the Salahuddin neighborhood near the city center. “This area is under heavy shelling with tanks, mortars and helicopter fire,” Halabi said.

At the same time, thousands of Syrian troops pulled out of a strategic plateau in the northwestern province of Idlib and headed toward Aleppo, opposition activists said, according to a Reuters report, adding to the sense that a showdown for control of the city was imminent.

Many civilians were caught up in the fighting. “At night, we hear shelling all the time, and in the day, we’re hearing the sound of bullets all over the city,” said a young woman in Aleppo who was reached by phone and spoke on the condition of anonymity to protect her safety.

The woman went to an airline office Tuesday to buy a ticket to Beirut, but clashes broke out and she had to escape the area on foot. “I wasn’t very scared at the beginning,” she said. “But today, when I was in the middle of shooting and I saw people running scared, I was scared, too. I want to get out of here now.”

Inmates in the central Aleppo prison also protested against the government Tuesday, and guards reportedly cut off water and electricity to the facility before attacking prisoners, according to al-Jazeera. The crackdown left at least eight prisoners dead, according to the Syrian Observatory for Human Rights, an opposition group based in Britain. The group reported that 86 people were killed across the country Tuesday, including 26 in Aleppo.

Soldiers and the pro-government shabiha militia also carried out a deadly attack on a mosque in the village of Sharia, near Hama, during the Ramadan evening prayers, leaving at least 30 dead, according to opposition groups.

The most high-profile defector from the Syrian government, Manaf Tlas, a brigadier general who was a close confidant of Assad’s, released a video statement that aired on al-Arabiya on Tuesday in which he called on Syrians to unite against the government. “We must all unite to serve Syria and promote stability in the country, rebuilding a free and democratic Syria,” he said.

The Syrian government suffered another loss Tuesday with what al-Jazeera reported was the defection of the country’s ambassador to Cyprus, Lamia al-Hariri.

Suzan Haidamous and Ahmed Ramadan contributed to this report.