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Zusammenfassung Im Blutausstrich lassen sich Erythrozyten von normalem und solche von stark vermindertem Katalasegehalt durch Verwendung von fluoreszierender Antikatalase unterscheiden. Mit dieser Methode konnte der früher erhobene Befund, wonach bei homozygoten Trägern des Enzymdefektes Akatalasie ein Pseudomosaizismus besteht, bestätigt werden. Bei der Untersuchung von Erythrozytenfraktionen verschiedener Dichte besteht eine Korrelation zwischen der Anzahl Retikulozyten und fluoreszierender Zellen. Dieser Befund passt zur Annahme, dass es sich bei der Katalaserestaktivität im Blut homozygoter Defektträger um eine instabile, jedoch antigenidentische Enzymvariante handelt. 相似文献
104.
Prinz M Heikenwalder M Junt T Schwarz P Glatzel M Heppner FL Fu YX Lipp M Aguzzi A 《Nature》2003,425(6961):957-962
Peripheral infection is the natural route of transmission in most prion diseases. Peripheral prion infection is followed by rapid prion replication in lymphoid organs, neuroinvasion and progressive neurological disease. Both immune cells and nerves are involved in pathogenesis, but the mechanisms of prion transfer from the immune to the nervous system are unknown. Here we show that ablation of the chemokine receptor CXCR5 juxtaposes follicular dendritic cells (FDCs) to major splenic nerves, and accelerates the transfer of intraperitoneally administered prions into the spinal cord. Neuroinvasion velocity correlated exclusively with the relative locations of FDCs and nerves: transfer of CXCR5-/- bone marrow to wild-type mice induced perineural FDCs and enhanced neuroinvasion, whereas reciprocal transfer to CXCR5-/- mice abolished them and restored normal efficiency of neuroinvasion. Suppression of lymphotoxin signalling depleted FDCs, abolished splenic infectivity, and suppressed acceleration of pathogenesis in CXCR5-/- mice. This suggests that prion neuroimmune transition occurs between FDCs and sympathetic nerves, and relative positioning of FDCs and nerves controls the efficiency of peripheral prion infection. 相似文献
105.
Recombinant adeno-associated virus serotype 2 (rAAV2) is a promising vector for gene therapy because it can achieve long-term stable transgene expression in animals and human subjects after direct administration of vectors into various target tissues. In the liver, although stable transgene expression primarily results from extrachromosomal vector genomes, a series of experiments has shown that vector genomes integrate into host chromosomes in hepatocytes at a low frequency. Despite the low integration efficiency, recent reports of retroviral insertional mutagenesis in mice and two human subjects have raised concerns about the potential for rAAV2-mediated insertional mutagenesis. Here we characterize rAAV2-targeted chromosomal integration sites isolated from selected or non-selected hepatocytes in vector-injected mouse livers. We document frequent chromosomal deletions of up to 2 kb at integration sites (14 of 14 integrations, 100%; most of the deletions were <0.3 kb) and preferred integration into genes (21 of 29 integrations, 72%). In addition, all of the targeted genes analyzed (20 of 20 targeted genes, 100%) were expressed in the liver. This is the first report to our knowledge on host chromosomal effects of rAAV2 integration in animals, and it provides insights into the nature of rAAV2 vector integration into chromosomes in quiescent somatic cells in animals and human subjects. 相似文献
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Ursin R Jennewein T Aspelmeyer M Kaltenbaek R Lindenthal M Walther P Zeilinger A 《Nature》2004,430(7002):849
Efficient long-distance quantum teleportation is crucial for quantum communication and quantum networking schemes. Here we describe the high-fidelity teleportation of photons over a distance of 600 metres across the River Danube in Vienna, with the optimal efficiency that can be achieved using linear optics. Our result is a step towards the implementation of a quantum repeater, which will enable pure entanglement to be shared between distant parties in a public environment and eventually on a worldwide scale. 相似文献
108.
Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking
Di Paolo G Moskowitz HS Gipson K Wenk MR Voronov S Obayashi M Flavell R Fitzsimonds RM Ryan TA De Camilli P 《Nature》2004,431(7007):415-422
Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) has an important function in cell regulation both as a precursor of second messenger molecules and by means of its direct interactions with cytosolic and membrane proteins. Biochemical studies have suggested a role for PtdIns(4,5)P2 in clathrin coat dynamics, and defects in its dephosphorylation at the synapse produce an accumulation of coated endocytic intermediates. However, the involvement of PtdIns(4,5)P2 in synaptic vesicle exocytosis remains unclear. Here, we show that decreased levels of PtdIns(4,5)P2 in the brain and an impairment of its depolarization-dependent synthesis in nerve terminals lead to early postnatal lethality and synaptic defects in mice. These include decreased frequency of miniature currents, enhanced synaptic depression, a smaller readily releasable pool of vesicles, delayed endocytosis and slower recycling kinetics. Our results demonstrate a critical role for PtdIns(4,5)P2 synthesis in the regulation of multiple steps of the synaptic vesicle cycle. 相似文献
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Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase 总被引:1,自引:0,他引:1
Thoma R Schulz-Gasch T D'Arcy B Benz J Aebi J Dehmlow H Hennig M Stihle M Ruf A 《Nature》2004,432(7013):118-122
In higher organisms the formation of the steroid scaffold is catalysed exclusively by the membrane-bound oxidosqualene cyclase (OSC; lanosterol synthase). In a highly selective cyclization reaction OSC forms lanosterol with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. Valuable data on the mechanism of the complex cyclization cascade have been collected during the past 50 years using suicide inhibitors, mutagenesis studies and homology modelling. Nevertheless it is still not fully understood how the enzyme catalyses the reaction. Because of the decisive role of OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. Here we present two crystal structures of the human membrane protein OSC: the target protein with an inhibitor that showed cholesterol lowering in vivo opens the way for the structure-based design of new OSC inhibitors. The complex with the reaction product lanosterol gives a clear picture of the way in which the enzyme achieves product specificity in this highly exothermic cyclization reaction. 相似文献