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AAAI, pp. 328\u2013336."},{"key":"ref23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0010-4825(95)00042-9","article-title":"Qualitative analysis of biochemical reaction systems","volume":"26","author":"VN Reddy","year":"1996","journal-title":"Computational Biology"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Heiner M, Koch I (2004) Petri net based models validation in systems biology. In: 25th International Conference on Application and Theory of Petri Nets (ICATPN), Springer-Verlag Berlin Heidelberg, LNCS. pp. 216\u2013237.","DOI":"10.1007\/978-3-540-27793-4_13"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Genrich H, Kuffner R, Voss K (2001) Executable Petri net models for the analysis of metabolic pathways. 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Springer, volume LNCS 5391, pp. 13\u201328.","DOI":"10.1007\/978-3-540-95885-7_2"},{"key":"ref29","unstructured":"Hecht M (2009). Modelling of signal transduction pathways. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.bio.ifi.lmu.de\/webfm_send\/340\" xlink:type=\"simple\">http:\/\/www.bio.ifi.lmu.de\/webfm_send\/340<\/ext-link>"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s12038-007-0011-6","article-title":"Modeling and simulation of signaling transduction in an apoptosis pathway by using Petri nets","volume":"32","author":"C Li","year":"2007","journal-title":"Journal of Biosciences"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1752-0509-2-76","article-title":"Rapidly exploring structural and dynamic properties of signaling networks using pathwayoracle","volume":"2","author":"D Ruths","year":"2008","journal-title":"BMC Systems Biology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e1000005","DOI":"10.1371\/journal.pcbi.1000005","article-title":"The signaling Petri net-based simulator: A non- parametric strategy for characterizing the dynamics of cell-specific signaling networks","volume":"4","author":"D Ruths","year":"2008","journal-title":"PLoS Computational Biology"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/0022-5193(69)90015-0","article-title":"Metabolic stability and epidenesis in randomly constructed genetic nets","volume":"22","author":"SA Kauffman","year":"1969","journal-title":"Journal of Theoretical Biology"},{"key":"ref34","first-page":"507","article-title":"Kinetic logic: a boolean approach to the analysis of complex regulatory systems","volume":"29","author":"R Thomas","year":"1979","journal-title":"Lecture Notes in Biomathematics"},{"key":"ref35","first-page":"17","article-title":"Identification of genetic networks from a small number of gene expression patterns under the boolean network model","volume":"4","author":"T Akutsu","year":"1999","journal-title":"Pacific Symposium on Biocomputing"},{"key":"ref36","article-title":"Termporal Boolean network models of generic networks and their inference from gene expression time series","volume":"11","author":"A Silvescu","year":"1997","journal-title":"Complex Systems"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1128\/MMBR.66.2.300-372.2002","article-title":"Osmotic stress signaling and osmoadaptation in yeasts","volume":"66","author":"S Hohmann","year":"2012","journal-title":"Microbiology and Molecular Biology Reviews"},{"key":"ref38","unstructured":"Peterson J (1981) Petri net theory and the modeling of systems. Upper Saddle River, NJ, USA: Prentice Hall PTR."},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Bobbio A (1990) System Modeling with Petri nets. Ph.D. thesis, Instituto Elettrotecnico Nazionale Galileo Ferraris, Torino, Italy.","DOI":"10.1007\/978-94-009-0649-5_6"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/bib\/bbm029","article-title":"Petri net modeling of biological networks","volume":"8","author":"C Chaouiya","year":"2007","journal-title":"Briefings in Bioinformatics"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/0021-9991(76)90041-3","article-title":"A general method for numerically simulating stochastic time evolution of coupled chemical reactions","volume":"22","author":"D Gillespie","year":"1976","journal-title":"Journal of Computational Physics"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Wang J (1998) Timed Petri nets: Theory and application, volume 39. 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