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"Like millions of people across the globe, my husband and I are outraged and heartbroken over the kidnapping of more than 200 Nigerian girls from their school dormitory in the middle of the night," Mrs. Obama said in the address.
"This unconscionable act was committed by a terrorist group determined to keep these girls from getting an education - grown men attempting to snuff out the aspirations of young girls."
Nigerian President Goodluck Jonathan said on Friday he believed the girls, abducted by militant Islamist group Boko Haram, were still in his country.
Militants stormed a secondary school in the village of Chibok, near the Cameroon border, on April 14, and kidnapped the girls, who were taking exams at the time. Fifty have since escaped, but more than 200 remain with the insurgents.
The United States offered this week to send a team of experts to Nigeria to support the government's response effort, which has been criticized for being slow.
"I want you to know that Barack has directed our government to do everything possible to support the Nigerian government's efforts to find these girls and bring them home," Mrs. Obama said.
"In these girls, Barack and I see our own daughters. We see their hopes, their dreams - and we can only imagine the anguish their parents are feeling right now."
The first lady noted that the school where the girls were abducted had been closed recently because of terrorist threats, but the girls insisted on coming back to take exams.
"They were so determined to move to the next level of their education...so determined to one day build careers of their own and make their families and communities proud," she said.
"And what happened in Nigeria was not an isolated incident. It's a story we see every day as girls around the world risk their lives to pursue their ambitions."