The article presents an infrastructure for supporting the semantic interoperability of biomedical resources based on the management (storing and inference-based querying) of their ontology-based annotations. This infrastructure consists of: (i) a repository to store and query ontology-based annotations, (ii) a knowledge base server with an inference engine to support the storage of and reasoning over ontologies used in the annotation of resources, (iii) a set of applications and services allowing interaction with the integrated repository and knowledge base. The infrastructure is being prototyped and developed and evaluated by the RICORDO project in support of the knowledge management of biomedical resources, including physiology and pharmacology models and associated clinical data.