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| 1501 |
| | | The 14-year-old Ismail I is enthroned as shah of a new Persian dynasty, the Safavids | |
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| 1501 |
| | | Michelangelo begins work in Florence on a tall thin slab of marble, which he transforms into David | |
|  | David Michelangelo
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| 1501 |
| | | Italian navigator Amerigo Vespucci sets sail from Lisbon to explore to the south of the New World | |
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| 1502 |
| | | Vasco da Gama wins a trading treaty for Portuguese merchants after bombarding the Indian port of Calicut into submission | |
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| 1503 |
| | | The marriage of James IV, king of Scotland, to Margaret Tudor, daughter of Henry VII, leads a century later to the Union of the Crowns | |
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| 1503 |
| | | Hieronymus Bosch paints the most detailed of his exotically surreal canvases, The Garden of Earthly Delights | |
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| 1503 |
| | | The Portuguese set up a trading post on the east African island of Zanzibar | |
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| 1504 |
| | | Babur captures Kabul, making it and eastern Afghanistan the first possession of the Mughal empire | |
|  | Babur in a garden
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| 1505 |
| | | The Portuguese establish a presence in Sri Lanka, trading in the island's crop of cinammon | |
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| c. 1505 |
| | | Leonardo captures the enigmatic smile of Lisa Gherardini, known now as the Mona Lisa | |
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