全文获取类型
收费全文 | 196篇 |
免费 | 12篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 2篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 8篇 |
2014年 | 5篇 |
2013年 | 11篇 |
2012年 | 16篇 |
2011年 | 17篇 |
2010年 | 6篇 |
2009年 | 7篇 |
2008年 | 10篇 |
2007年 | 11篇 |
2006年 | 10篇 |
2005年 | 12篇 |
2004年 | 7篇 |
2003年 | 8篇 |
2002年 | 4篇 |
2001年 | 6篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1977年 | 1篇 |
1974年 | 2篇 |
1970年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有208条查询结果,搜索用时 15 毫秒
101.
102.
The fruit fly, Drosophila melanogaster, innately avoids even low levels of CO2. CO2 is part of the so-called Drosophila stress odor produced by stressed flies, but also a byproduct of fermenting fruit, a main food source, making the strong avoidance behavior somewhat surprising. Therefore, we addressed whether feeding states might influence the fly’s behavior and processing of CO2. In a recent report, we showed that this innate behavior is differentially processed and modified according to the feeding state of the fly. Interestingly, we found that hungry flies require the function of the mushroom body, a higher brain center required for olfactory learning and memory, but thought to be dispensable for innate olfactory behaviors. In addition, we anatomically and functionally characterized a novel bilateral projection neuron connecting the CO2 sensory input to the mushroom body. This neuron was essential for processing of CO2 in the starved fly but not in the fed fly. In this Extra View article, we provide evidence for the potential involvement of the neuromodulator dopamine in state-dependent CO2 avoidance behavior. Taken together, our work demonstrates that CO2 avoidance behavior is mediated by alternative neural pathways in a context-dependent manner. Furthermore, it shows that the mushroom body is not only involved in processing of learned olfactory behavior, as previously suggested, but also in context-dependent innate olfaction. 相似文献
103.
Augusto O Bonini MG Amanso AM Linares E Santos CC De Menezes SL 《Free radical biology & medicine》2002,32(9):841-859
Nitrogen dioxide and carbonate radical anion have received sporadic attention thus far from biological investigators. However, accumulating data on the biochemical reactions of nitric oxide and its derived oxidants suggest that these radicals may play a role in various pathophysiological processes. These potential roles are also indicated by recent studies on the high efficiency of urate and nitroxides in protecting cells and whole animals against the injury associated with conditions of excessive nitric oxide production. The high protective effects of these antioxidants are incompletely defined at the mechanistic level but some of them can be explained by their efficiency in scavenging peroxynitrite-derived radicals, particularly nitrogen dioxide and carbonate radical anion. In this review, we provide a framework for this hypothesis and discuss the potential sources and properties of these radicals that are likely to become increasingly recognized as important mediators of biological processes. 相似文献
104.
105.
106.
D Scarpi D Cirelli C Matrone G Castronovo P Rosini E G Occhiato F Romano L Bartali A M Clemente G Bottegoni A Cavalli G De Chiara P Bonini P Calissano A T Palamara E Garaci M G Torcia A Guarna F Cozzolino 《Cell death & disease》2012,3(7):e339
Exploitation of the biologic activity of neurotrophins is desirable for medical purposes, but their protein nature intrinsically bears adverse pharmacokinetic properties. Here, we report synthesis and biologic characterization of a novel class of low molecular weight, non-peptidic compounds with NGF (nerve growth factor)-mimetic properties. MT2, a representative compound, bound to Trk (tropomyosin kinase receptor)A chain on NGF-sensitive cells, as well as in cell-free assays, at nanomolar concentrations and induced TrkA autophosphorylation and receptor-mediated internalization. MT2 binding involved at least two amino-acid residues within TrkA molecule. Like NGF, MT2 increased phosphorylation of extracellular signal-regulated kinase1/2 and Akt proteins and production of MKP-1 phosphatase (dual specificity phosphatase 1), modulated p38 mitogen-activated protein kinase activation, sustained survival of serum-starved PC12 or RDG cells, and promoted their differentiation. However, the intensity of such responses was heterogenous, as the ability of maintaining survival was equally possessed by NGF and MT2, whereas the induction of differentiation was expressed at definitely lower levels by the mimetic. Analysis of TrkA autophosphorylation patterns induced by MT2 revealed a strong tyrosine (Tyr)490 and a limited Tyr785 and Tyr674/675 activation, findings coherent with the observed functional divarication. Consistently, in an NGF-deprived rat hippocampal neuronal model of Alzheimer Disease, MT2 could correct the biochemical abnormalities and sustain cell survival. Thus, NGF mimetics may reveal interesting investigational tools in neurobiology, as well as promising drug candidates. 相似文献
107.
Provasi E Genovese P Lombardo A Magnani Z Liu PQ Reik A Chu V Paschon DE Zhang L Kuball J Camisa B Bondanza A Casorati G Ponzoni M Ciceri F Bordignon C Greenberg PD Holmes MC Gregory PD Naldini L Bonini C 《Nature medicine》2012,18(5):807-815
The transfer of high-avidity T cell receptor (TCR) genes isolated from rare tumor-specific lymphocytes into polyclonal T cells is an attractive cancer immunotherapy strategy. However, TCR gene transfer results in competition for surface expression and inappropriate pairing between the exogenous and endogenous TCR chains, resulting in suboptimal activity and potentially harmful unpredicted antigen specificities of the resultant TCRs. We designed zinc-finger nucleases (ZFNs) that promoted the disruption of endogenous TCR β- and α-chain genes. Lymphocytes treated with ZFNs lacked surface expression of CD3-TCR and expanded with the addition of interleukin-7 (IL-7) and IL-15. After lentiviral transfer of a TCR specific for the Wilms tumor 1 (WT1) antigen, these TCR-edited cells expressed the new TCR at high levels, were easily expanded to near purity and were superior at specific antigen recognition compared to donor-matched, unedited TCR-transferred cells. In contrast to unedited TCR-transferred cells, the TCR-edited lymphocytes did not mediate off-target reactivity while maintaining their anti-tumor activity in vivo, thus showing that complete editing of T cell specificity generates tumor-specific lymphocytes with improved biosafety profiles. 相似文献
108.
Watson MR Lagow RD Xu K Zhang B Bonini NM 《The Journal of biological chemistry》2008,283(36):24972-24981
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that leads to loss of motor function and early death. About 5% of cases are inherited, with the majority of identified linkages in the gene encoding copper, zinc-superoxide dismutase (SOD1). Strong evidence indicates that the SOD1 mutations confer dominant toxicity on the protein. To provide new insight into mechanisms of ALS, we have generated and characterized a model for familial ALS in Drosophila with transgenic expression of human SOD1. Expression of wild type or disease-linked (A4V, G85R) mutants of human SOD1 selectively in motor neurons induced progressive climbing deficits. These effects were accompanied by defective neural circuit electrophysiology, focal accumulation of human SOD1 protein in motor neurons, and a stress response in surrounding glia. However, toxicity was not associated with oligomerization of SOD1 and did not lead to neuronal loss. These studies uncover cell-autonomous injury by SOD1 to motor neurons in vivo, as well as non-autonomous effects on glia, and provide the foundation for new insight into injury and protection of motor neurons in ALS. 相似文献
109.
Ines Capeleti Edicleia Aparecida Bonini Maria de Lourdes Lucio Ferrarese Aline Cristina Neres Teixeira Francisco Carlos Krzyzanowski Osvaldo Ferrarese-Filho 《Acta Physiologiae Plantarum》2005,27(1):103-108
Mechanical damage is one of the causes of great loss in the quality of soybean seeds during harvest and processing. Considerable
interest exists in the lignin since its deposition in the seed coat tissue provides mechanical resistance and protects the
cell against microorganisms. In addition, peroxidases might be involved in the oxidation of cinnamyl alcohols prior to their
polymerization during lignin formation. Thus, the aim of the present work was to analyze the lignin contents and peroxidases
activities of six Brazilian soybean cultivars (Savana, Paranagoiana, FT-10, Santa Rosa, Doko and Paraná) and their relationships
with the mechanical damage. Results showed that the lignin content and peroxidase activity in the seed coat significantly
differed among the soybean cultivars. Cultivars Doko and Paraná had the highest contents of lignin and peroxidases activities
while the other cultivars had lowest lignin contents and enzyme activities. Lignin content and peroxidase activity may be
reasonable indicators of resistance to mechanical damage in soybean seeds. 相似文献
110.