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Zhao H Li CC Pardo J Chu PC Liao CX Huang J Dong JG Zhou X Huang Q Huang B Bennett MK Molineaux SM Lu H Daniel-Issakani S Payan DG Masuda ES 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(9):5288-5297
TRAC-1 (T cell RING (really interesting new gene) protein identified in activation screen) is a novel E3 ubiquitin ligase identified from a retroviral vector-based T cell surface activation marker screen. The C-terminal truncated TRAC-1 specifically inhibited anti-TCR-mediated CD69 up-regulation in Jurkat cells, a human T leukemic cell line. In this study, we show that TRAC-1 is a RING finger ubiquitin E3 ligase with highest expression in lymphoid tissues. Point mutations that disrupt the Zn(2+)-chelating ability of its amino-terminal RING finger domain abolished TRAC-1's ligase activity and the dominant inhibitory effect of C-terminal truncated TRAC-1 on TCR stimulation. The results of in vitro biochemical studies indicate that TRAC-1 can stimulate the formation of both K48- and K63-linked polyubiquitin chains and therefore could potentially activate both degradative and regulatory ubiquitin-dependent pathways. Antisense oligonucleotides to TRAC-1 specifically reduced TRAC-1 mRNA levels in Jurkat and primary T cells and inhibited their activation in response to TCR cross-linking. Collectively, these results indicate that the E3 ubiquitin ligase TRAC-1 functions as a positive regulator of T cell activation. 相似文献
124.
Parveen Kaur Parmar Charlene C. Barina Sharon Low Kyaw Thura Tun Conrad Otterness Pue P. Mhote Saw Nay Htoo Saw Win Kyaw Nai Aye Lwin Cynthia Maung Naw Merry Moo Eh Kalu Shwe Oo Daniel Reh Nai Chay Mon Nakul Singh Ravi Goyal Adam K. Richards 《PloS one》2015,10(5)
BackgroundMyanmar transitioned to a nominally civilian parliamentary government in March 2011. Qualitative reports suggest that exposure to violence and displacement has declined while international assistance for health services has increased. An assessment of the impact of these changes on the health and human rights situation has not been published.ConclusionThis large survey of health and human rights demonstrates that two years after political transition, vulnerable populations of eastern Myanmar are less likely to experience human rights violations compared to previous surveys. However, access to health services remains constrained, and risk of disease and death remains higher than the country as a whole. Efforts to address these poor health indicators should prioritize support for populations that remain outside the scope of most formal government and donor programs. 相似文献
125.
Few finance theories consider the influence of "skewness" (or large and asymmetric but unlikely outcomes) on financial choice. We investigated the impact of skewed gambles on subjects' neural activity, self-reported affective responses, and subsequent preferences using functional magnetic resonance imaging (FMRI). Neurally, skewed gambles elicited more anterior insula activation than symmetric gambles equated for expected value and variance, and positively skewed gambles also specifically elicited more nucleus accumbens (NAcc) activation than negatively skewed gambles. Affectively, positively skewed gambles elicited more positive arousal and negatively skewed gambles elicited more negative arousal than symmetric gambles equated for expected value and variance. Subjects also preferred positively skewed gambles more, but negatively skewed gambles less than symmetric gambles of equal expected value. Individual differences in both NAcc activity and positive arousal predicted preferences for positively skewed gambles. These findings support an anticipatory affect account in which statistical properties of gambles--including skewness--can influence neural activity, affective responses, and ultimately, choice. 相似文献
126.
Background
Prolonged sitting is associated with increased weight and higher risks for abdominal obesity, dyslipidaemia, hyperglycaemia and hypertension among the adult population. This has been well documented in the West, but studies on these associations are lacking in developing countries, including Malaysia.Objective
This cross-sectional study aimed to examine the joint association of sitting time and physical activity with metabolic risk factors among middle-aged working adults.Methodology
A total of 686 Malay men and women participated (mean age 45.9±6.5 years). Metabolic syndrome was diagnosed from the modified NCEP ATP III criteria. Self-reported sitting time was obtained with the validated Malay version of the International Physical Activity Questionnaire. Participants were asked about their time spent sitting during travel in a motor vehicle, e.g., car, motorcycle or bus, over the preceding 7 days. Logistic regression was used to estimate the odds ratio with the confidence interval for the combined effects of sitting quartiles and physical activity categories with metabolic risk factors.Results/Significance
The prevalence of metabolic syndrome among our participants was 31.9%. Their average total sitting time (including transportation) was 7.6±2.4 h/day. After we adjusted for gender and educational level, higher sitting quartiles and physically inactive groups were associated with higher odds for metabolic syndrome compared with the referent group (sitting <6 h/day and physically active). In the physically active stratum, the odds for metabolic syndrome in participants who sat ≥9.3 h/day was 3.8 times that of participants who sat <6 h/day. Both higher sitting quartiles and insufficient physical activity were associated with adverse effects on abdominal obesity, hypertriglyceridemia and hyperglycaemia.Conclusion
In joint analyses of sitting time and physical activity, higher sitting time and insufficient physical activity were deleteriously associated with odds for metabolic risk factors in middle-aged Malay men and women. 相似文献127.
Mitochondria can regenerate ascorbic acid from its oxidized forms, which may help to maintain the vitamin both in mitochondria and in the cytoplasm. In this work, we sought to determine the site and mechanism of mitochondrial ascorbate recycling from dehydroascorbic acid. Rat skeletal muscle mitochondria incubated for 3 h at 37 degrees C with 500 microM dehydroascorbic acid and energy substrates maintained ascorbate concentrations more than twice those observed in the absence of substrate. Succinate-dependent mitochondrial reduction of dehydroascorbic acid was blocked by inhibitors of mitochondrial Complexes II and III. Neither cytochrome c nor the outer mitochondrial membrane were necessary for the effect. The ascorbate radical was generated by mitochondria during treatment with dehydroascorbic acid and was abolished by ferricyanide, which does not penetrate the mitochondrial inner membrane. Together, these results show that energy substrate-dependent ascorbate recycling from dehydroascorbic acid involves an externally exposed portion of mitochondrial complex III. 相似文献
128.
Background
Thymic function is altered in HIV infection and characterized by dysregulation of the thymic epithelial network, reduced thymic output and ultimately an impaired naïve T-cell pool. The IL-7/IL-7 receptor (IL-7R) signalling pathway is critical for the maturation and differentiation of thymocytes. HIV infection is associated with a decrease in IL-7Rα (CD127) expression and impaired CD127 signalling in circulating CD8+ T-cells; however, little is known about the effect of HIV on CD127 expression and IL-7 activity in the thymus. Therefore, the effect of in vitro HIV infection on CD127 expression and IL-7-mediated function in thymocytes was investigated.Findings
In vitro HIV infection of thymocytes did not affect CD127 expression on either total thymocytes or on single positive CD4 or single positive CD8 subsets. However, HIV infection resulted in a decrease in the level of IL-7-induced STAT-5 phosphorylation and Bcl-2 expression in unfractionated thymocytes.Conclusion
These findings indicate that HIV infection alters IL-7 responsiveness of thymocytes by a mechanism other than CD127 downregulation and potentially explain the disruption in thymopoiesis observed in HIV infection. 相似文献129.
Travis E. Van Leeuwen David Cote Christina Pretty Joseph Townley Rebecca Poole Brian Dempson Tomas J. Bird Charlene Kippenhuck Corey Morris 《Journal of fish biology》2021,99(6):2066-2070
We describe observations of sea lamprey (Petromyzon marinus) and striped bass (Morone saxatilis) incursions into Labrador, Canada. While P. marinus have been periodically observed in similar latitudes, their numbers have conspicuously increased in estuarine environments in 2020. In contrast, M. saxatilis were not observed from Labrador until 2017 but appear to be declining after the initial surge in abundance that peaked in 2018. It remains unclear whether spawning populations of either species exist. Given the potential to negatively affect species of commercial and cultural importance through predation, follow-up surveys are warranted. 相似文献
130.
McCafferty GP Pullen MA Wu C Edwards RM Allen MJ Woollard PM Borthwick AD Liddle J Hickey DM Brooks DP Westfall TD 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(1):R299-R305
Spontaneous and induced uterine contractions in the rat were found to be inhibited by a novel and selective oxytocin receptor antagonist GSK221149A (3R,6R)-3-Indan-2-yl-1-[(1R)-1-(2-methyl-1,3-oxazol-4-yl)-2-morpholin-4-yl-2-oxoethyl]-6-[(1S)-1-methylpropyl]-2,5-piperazinedione. GSK221149A displayed nanomolar affinity (K(i) = 0.65 nM) for human recombinant oxytocin receptors with >1,400-fold selectivity over human V1a, V1b, and V2 receptors. GSK221149A had similar affinity (K(i) = 4.1 nM) and selectivity for native oxytocin receptors from rat and produced a functional, competitive block of oxytocin-induced contractions in isolated rat myometrial strips with a pA(2) value of 8.18. Intravenous administration of GSK221149A produced a dose-dependent decrease in oxytocin-induced uterine contractions in anesthetized rats with an ID(50) = 0.27 +/- 0.60 mg/kg (corresponding plasma concentrations were 88 ng/ml). Oral administration of GSK221149A (5 mg/kg) was effective in inhibiting oxytocin-induced uterine contractions after single and multiple (4-day) dosing. Spontaneous uterine contractions in late-term pregnant rats (19-21 days gestation) were significantly reduced by intravenous administration of 0.3 mg/kg of GSK221149A. These results provide further evidence that selective oxytocin receptor antagonism may offer an effective treatment for preterm labor. 相似文献