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101.
Anergy, IFN-gamma production, and apoptosis in terminal infection of mice with Mycobacterium avium. 总被引:4,自引:0,他引:4
We have followed the course of experimental infection of mice with Mycobacterium avium over an extended period, assessing bacterial numbers and T cell responsiveness. When mice were infected intranasally, bacteria spread to the spleen and liver, but remained in highest numbers in the lungs. Both CD4+ and CD8+ T cells, assayed at any time from 6-28 wk after infection, produced IFN-gamma. After initial rapid growth, bacterial numbers slowly increased from approximately 107 at 6 wk to more than 5 x 108 at 28 wk, indicating that the resistance mechanisms so generated were not adequate to contain the infection. During infection, apoptosis of both CD4+ and CD8+ T cells, measured immediately ex vivo by staining with Annexin V, increased steadily. With some individual exceptions, there was a close correlation between apoptosis of CD4+ cells and level of IFN-gamma production by cultured spleen cells. By 34 wk postinfection, there was an abrupt cessation of IFN-gamma production. No IL-4 was detected, ruling out a switch to Th2 profile. Subsequently, bacterial numbers increased still further to >5 x 109 per lung, and the mice lost body weight and would have died if not killed for experimental or humane reasons. The possibility that T cells exposed over this prolonged period to extremely high doses of Ag may become tolerant by a process of terminal differentiation is discussed. 相似文献
102.
Eric A. Tanifum Alexander Y. Kots Byung-Kwon Choi Ferid Murad Scott R. Gilbertson 《Bioorganic & medicinal chemistry letters》2009,19(11):3067-3071
A series of pyridopyrimidine derivatives were synthesized and evaluated for their ability to inhibit cyclic nucleotide synthesis in the presence of stable toxin a of Escherichia coli. The structure activity relationships around the basic core structure were examined and examples with better activity and potentially better pharmacological properties are presented. 相似文献
103.
104.
This report describes a within-subjects comparison of the reinforcing effects of food and display on a single response, key pecking. Three male pigeons socially isolated and food deprived for 22 hr pecked a key-light when pecks resulted in a brief sighting of their respective mates. Pecks to a second key-light concurrently available resulted in brief food rewards. Responses to the female key had a greater latency than responses to the food key, irrespective of the nature of the preceding reinforcement. The two responses also differed in their form and in the extent to which they were accompanied by other behaviours performed around the key-lights. This is discussed in terms of both response-reinforcer interaction and the intrusion of Pavlovian conditioning effects. 相似文献
105.
Prostaglandin E2 (PGE2)-induced discocyte → echinocytic transformation has no effect om the viscosity or osmotic fragility of normal or stickle cell erythrocytes. Membrane permeability, reflected, reflected as potassium efflux, is significantly affected in normal erythrocytes when >90% of the cells are morphologically transformed to the enchinocytic III stage (PGE2 concentration of 1–2×106 ng/ml blood). This potassium loos is significant in sickle erythrocytes when 50–70% of the cell population has been transformed (PGE2 concentration, 5×105 ng/ml blood). This change in membrane permeability reprensents one-half to one-third the flux that occurs with sickling (i.e., >80% of the erythrocytes sickled). 相似文献
106.
Biomphalaria glabrata and Stagnicola palustris were raised in aquaria under crowded and uncrowded conditions. Measurements of greatest shell diameter were taken at regular intervals. Von Bertalanffy and logistic growth curves were fitted by least squares and maximum likelihood methods. The resulting parameter estimates produced better fits for the logistic equation than for the von Bertalanffy equation. 相似文献
107.
108.
A simple procedure is described for the qualitative and quantitative analysis of alkyl α-glycerol ethers as their corresponding alkoxy acetaldehydes. This method is advantageous in that the same derivative may be utilized for both quantitative and qualitative analysis. Moreover, the sensitivity of this procedure is greater than previously published spectrophotometric methods. 相似文献
109.
Emma R. Job Barbara Bottazzi Brad Gilbertson Kathryn M. Edenborough Lorena E. Brown Alberto Mantovani Andrew G. Brooks Patrick C. Reading 《PloS one》2013,8(3)
Members of the pentraxin family, including PTX3 and serum amyloid P component (SAP), have been reported to play a role in innate host defence against a range of microbial pathogens, yet little is known regarding their antiviral activities. In this study, we demonstrate that human SAP binds to human influenza A virus (IAV) strains and mediates a range of antiviral activities, including inhibition of IAV-induced hemagglutination (HA), neutralization of virus infectivity and inhibition of the enzymatic activity of the viral neuraminidase (NA). Characterization of the anti-IAV activity of SAP after periodate or bacterial sialidase treatment demonstrated that α(2,6)-linked sialic acid residues on the glycosidic moiety of SAP are critical for recognition by the HA of susceptible IAV strains. Other proteins of the innate immune system, namely human surfactant protein A and porcine surfactant protein D, have been reported to express sialylated glycans which facilitate inhibition of particular IAV strains, yet the specific viral determinants for recognition of these inhibitors have not been defined. Herein, we have selected virus mutants in the presence of human SAP and identified specific residues in the receptor-binding pocket of the viral HA which are critical for recognition and therefore susceptibility to the antiviral activities of SAP. Given the widespread expression of α(2,6)-linked sialic acid in the human respiratory tract, we propose that SAP may act as an effective receptor mimic to limit IAV infection of airway epithelial cells. 相似文献
110.
Catherine E. Myers Ahmed A. Moustafa Jony Sheynin Kirsten M. VanMeenen Mark W. Gilbertson Scott P. Orr Kevin D. Beck Kevin C. H. Pang Richard J. Servatius 《PloS one》2013,8(8)
Post-traumatic stress disorder (PTSD) symptoms include behavioral avoidance which is acquired and tends to increase with time. This avoidance may represent a general learning bias; indeed, individuals with PTSD are often faster than controls on acquiring conditioned responses based on physiologically-aversive feedback. However, it is not clear whether this learning bias extends to cognitive feedback, or to learning from both reward and punishment. Here, male veterans with self-reported current, severe PTSD symptoms (PTSS group) or with few or no PTSD symptoms (control group) completed a probabilistic classification task that included both reward-based and punishment-based trials, where feedback could take the form of reward, punishment, or an ambiguous “no-feedback” outcome that could signal either successful avoidance of punishment or failure to obtain reward. The PTSS group outperformed the control group in total points obtained; the PTSS group specifically performed better than the control group on reward-based trials, with no difference on punishment-based trials. To better understand possible mechanisms underlying observed performance, we used a reinforcement learning model of the task, and applied maximum likelihood estimation techniques to derive estimated parameters describing individual participants’ behavior. Estimations of the reinforcement value of the no-feedback outcome were significantly greater in the control group than the PTSS group, suggesting that the control group was more likely to value this outcome as positively reinforcing (i.e., signaling successful avoidance of punishment). This is consistent with the control group’s generally poorer performance on reward trials, where reward feedback was to be obtained in preference to the no-feedback outcome. Differences in the interpretation of ambiguous feedback may contribute to the facilitated reinforcement learning often observed in PTSD patients, and may in turn provide new insight into how pathological behaviors are acquired and maintained in PTSD. 相似文献