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Ekaterina Maidji Galina Kosikova Pheroze Joshi Cheryl A. Stoddart 《Journal of virology》2012,86(23):12795-12805
Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and life-threatening lung-associated diseases in premature infants and immunocompromised children. Although the fetal lung is a major target organ of the virus, HCMV lung pathogenesis has remained unexplored, possibly as a result of extreme host range restriction. To overcome this hurdle, we generated a SCID-hu lung mouse model that closely recapitulates the discrete stages of human lung development in utero. Human fetal lung tissue was implanted into severe combined immunodeficient (CB17-scid) mice and inoculated by direct injection with the VR1814 clinical isolate of HCMV. Virus replication in the fetal lung was assessed by the quantification of infectious virus titers and HCMV genome copies and the detection of HCMV proteins by immunohistochemistry and Western blotting. We show that HCMV efficiently replicated in the lung implants during a 2-week period, forming large viral lesions. The virus productively infected alveolar epithelial and mesenchymal cells, imitating congenital infection of the fetal lung. HCMV replication triggered apoptosis near and within the viral lesions and impaired the production of surfactant proteins in the alveolar epithelium. Our findings highlight that congenital and neonatal HCMV infection can adversely impact lung development, leading to pneumonia and acute lung injury. We have successfully developed a small-animal model that closely recapitulates fetal and neonatal lung development and provides a valuable, biologically relevant tool for an understanding of the lung pathogenesis of HCMV as well as other human respiratory viruses. Additionally, this model would greatly facilitate the development and testing of new antiviral therapies for HCMV along with select human pulmonary pathogens. 相似文献
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A review of experimental data documenting that domestication of animals is associated with hereditary reorganization of neuro-endocrine mechanisms, responsible for basic processes of ontogeny, is presented. The data demonstrated changes in gonadal and pituitary-adrenal systems in domesticated animals. Analysis of evidence that selection for low aggressiveness towards man is, in fact, the selection for definite activity of brain neurotransmitters regulating aggressive behaviour and emotional stress response has been carried out. Supposed role of modifications in the mechanisms of domestication is discussed. 相似文献
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Comparative genetic analysis of social dominance in micropopulations of male mice as well as noradrenaline and dopamine levels in brain was carried out. The RT male mice had maximal level of social dominance and the greatest content of brain catecholamines. It is suggested that the capacity for social dominance may depend on the function of the central catecholamine neurons. This suggestion has been confirmed by the data obtained both for interstrain and intrastrain relations between social dominance and catecholamine levels. 相似文献
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L I Serova O N Kozlova E V Naumenko 《Zhurnal vysshe? nervno? deiatelnosti imeni I P Pavlova》1991,41(1):79-84
Influence of genotype and such individual characteristics as locomotor and exploratory activity, aggressiveness and emotionality, was studied in male mice. Males F1 and males of the parent line PT had high level of social dominance. F1 had high level of aggressiveness, and low emotionality, medium level of locomotor and exploratory activity. Significance of these individual behavioural characteristics for dominant behaviour is discussed. 相似文献
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Membrane preparations, capable of high rates of respiration-linked ATP synthesis, have been obtained from a gram-positive methylotrophic bacterium Bacillus sp. MGA3. NADH, succinate, reduced TMPD and methanol were shown to be suitable substrates for the oxidative phosphorylation. Esterification of orthophosphate was dependent on electron transfer, as evidenced by the requirement for both substrate and oxygen. Phosphorylation was also dependent on ADP and was destroyed by boiling the membrane preparation. The phosphorylation was markedly uncoupled by carbonyl cyanide p-(trichloromethoxy)-phenylhydrazone (CCCP) and was inhibited by N,N-dicyclohexylcarbodiimide (DCCD). KCN caused strong inhibition of substrate oxidation as well as phosphorylation for all substrates tested. Rotenone, amytal and antimycin A caused inhibition when NADH or methanol were used as substrates. Antimycin A inhibited respiration and ATP synthesis with succinate as substrate and had no effect on ascorbate —N,N,N,N-tetramethyl-p-phenylenediimide (TMPD) oxidation by membrane preparations of Bacillus sp. MGA3. P/O ratios determined were 2.4 with NADH, 1.7 with succinate and 0.8 with reduced TMPD. The measured P/O ratio with methanol-oxidizing system was similar to that with NADH (about 2.4).Abbreviations CCCP
Carbonyl cyanide p-(trichloromethoxy)-phenylhydrazone
- DCCD
N,N-dicyclohexylcarbodiimide
- TMPD
N,N,N,N-tetramethyl-p-phenylenediimide
- Q
ubiquinone Q 相似文献
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