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Science 1 March 2002:
Vol. 295. no. 5560, pp. 1662 - 1664
DOI: 10.1126/science.1069492
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Review

Systems Biology: A Brief Overview

Hiroaki Kitano

To understand biology at the system level, we must examine the structure and dynamics of cellular and organismal function, rather than the characteristics of isolated parts of a cell or organism. Properties of systems, such as robustness, emerge as central issues, and understanding these properties may have an impact on the future of medicine. However, many breakthroughs in experimental devices, advanced software, and analytical methods are required before the achievements of systems biology can live up to their much-touted potential.

Sony Computer Science Laboratories, Inc., 3-14-13 Higashi-Gotanda, Shinagawa, Tokyo 141-0022, Japan, and Kitano Symbiotic Systems Project, ERATO, JST, and the Systems Biology Institute, Suite 6A, M31, 6-31-15 Jingumae, Shibuya, Tokyo 150-0001, Japan. E-mail: kitano{at}csl.sony.co.jp

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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(2003)
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   Full Text »    PDF »
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   Full Text »    PDF »
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   Full Text »    PDF »
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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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