全文获取类型
收费全文 | 331篇 |
免费 | 27篇 |
出版年
2023年 | 2篇 |
2021年 | 3篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 8篇 |
2016年 | 5篇 |
2015年 | 11篇 |
2014年 | 10篇 |
2013年 | 19篇 |
2012年 | 30篇 |
2011年 | 24篇 |
2010年 | 24篇 |
2009年 | 16篇 |
2008年 | 19篇 |
2007年 | 11篇 |
2006年 | 23篇 |
2005年 | 17篇 |
2004年 | 14篇 |
2003年 | 18篇 |
2002年 | 17篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 7篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1974年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有358条查询结果,搜索用时 500 毫秒
151.
Laura Camardella Mario Romano Guido di Prisco Fiorella Descalzi-Cancedda 《Biochemical and biophysical research communications》1981,103(4):1384-1389
Reaction of glucose-6-phosphate dehydrogenase from human erythrocytes with pyridoxal-5′-phosphate causes 80% loss of activity. The substrate glucose-6-phosphate fully protects the enzyme against this inhibition, which is reversible upon dilution, but becomes irreversible after treatment with NaBH4. We presume that pyridoxal-5′-phosphate forms with the enzyme a Schiff base which is reduced by NaBH4. One mole of N-?-pyridoxyl-lysine is formed per mole of enzyme subunit when the remaining activity reaches its minimal level of 20%. 相似文献
152.
153.
154.
155.
156.
Inhalation of anthrax spores rapidly develops into a deadly bacteraemia and toxaemia. Anthrax toxins include the lethal factor (LF), a mitogen-activated protein kinase (MAPK)-kinase-specific metalloprotease, which acts in the cell cytosol and plays a major part in anthrax pathogenesis. Recently, screening methods have led to the discovery of LF inhibitors that are membrane permeable. This will pave the way for design of novel anthrax therapeutics that are capable of inhibiting the metalloprotease activity of LF in vivo. 相似文献
157.
Nitric Oxide Is Involved in Cadmium-Induced Programmed Cell Death in Arabidopsis Suspension Cultures 总被引:3,自引:0,他引:3 下载免费PDF全文
Roberto De Michele Emanuela Vurro Chiara Rigo Alex Costa Lisa Elviri Marilena Di Valentin Maria Careri Michela Zottini Luigi Sanità di Toppi Fiorella Lo Schiavo 《Plant physiology》2009,150(1):217-228
Exposure to cadmium (Cd2+) can result in cell death, but the molecular mechanisms of Cd2+ cytotoxicity in plants are not fully understood. Here, we show that Arabidopsis (Arabidopsis thaliana) cell suspension cultures underwent a process of programmed cell death when exposed to 100 and 150 μm CdCl2 and that this process resembled an accelerated senescence, as suggested by the expression of the marker senescence-associated gene12 (SAG12). CdCl2 treatment was accompanied by a rapid increase in nitric oxide (NO) and phytochelatin synthesis, which continued to be high as long as cells remained viable. Hydrogen peroxide production was a later event and preceded the rise of cell death by about 24 h. Inhibition of NO synthesis by NG-monomethyl-arginine monoacetate resulted in partial prevention of hydrogen peroxide increase, SAG12 expression, and mortality, indicating that NO is actually required for Cd2+-induced cell death. NO also modulated the extent of phytochelatin content, and possibly their function, by S-nitrosylation. These results shed light on the signaling events controlling Cd2+ cytotoxicity in plants.Cadmium (Cd2+) is a heavy metal with a long biological half-life, and its presence as a pollutant in agricultural soil is due mainly to anthropogenic activities. It is rapidly taken up by roots and enters the food chain, resulting in toxicity for both plants and animals (for review, see Sanità di Toppi and Gabbrielli, 1999). Cd2+ inhibits seed germination, decreases plant growth and photosynthesis, and impairs the distribution of nutrients. Overall, the symptoms of chronic exposure to sublethal amounts of Cd2+ mimic premature senescence (Rascio et al., 1993; McCarthy et al., 2001; Sandalio et al., 2001; Rodriguez-Serrano et al., 2006). Depending on the concentration, Cd2+ treatment of tobacco (Nicotiana tabacum) cell cultures and onion (Allium cepa) roots eventually triggers either necrosis or programmed cell death (PCD; Fojtovà and Kovařik, 2000; Behboodi and Samadi, 2004).Although Cd2+ is an environmental threat, the mechanisms by which it exerts its toxic effects in plants are not fully understood. In plant cells, Cd2+ is believed to enter through Fe2+, Ca2+, and Zn2+ transporters/channels (Clemens, 2006). Once in the cytosol, Cd2+ stimulates the production of phytochelatins (PCs), a glutathione-derived class of peptides containing repeated units of Glu and Cys, which bind the metal ions and transport them into the vacuole (Sanità di Toppi and Gabbrielli, 1999). Strong evidence exists that high (millimolar) concentrations of Cd2+ induce reactive oxygen species (ROS) bursts in plants, which might have a role in signaling and/or degenerative steps leading to cell death (Piqueras et al., 1999; Olmos et al., 2003; Cho and Seo, 2005; Garnier et al., 2006). Treatment with a lower, nontoxic Cd2+ concentration also caused increase in ROS production in pea (Pisum sativum) leaves and roots (Sandalio et al., 2001; Romero-Puertas et al., 2004; Rodriguez-Serrano et al., 2006) and Arabidopsis (Arabidopsis thaliana) cell cultures (Horemans et al., 2007).Nitric oxide (NO) is a gaseous reactive molecule with a pivotal signaling role in many developmental and response processes (for review, see Neill et al., 2003; Besson-Bard et al., 2008). In plants, it can be synthesized via several routes, either enzymatically or by chemical reduction of nitrite. Nitrate reductase and a root-specific plasma membrane nitrite-NO reductase also utilize nitrite as substrate. In animals, nitric oxide synthase (NOS) converts l-Arg into NO and l-citrulline. Although no plant NOS has been unambiguously identified yet, activity assays and pharmacological evidence suggests the existence of a NOS-like counterpart in plants. Depending on its concentration and possibly on the timing and localization of its production, NO can either act as an antioxidant or promote PCD, often in concert with ROS (Delledonne et al., 2001; Beligni et al., 2002; de Pinto et al., 2006). Extensive research has shown that NO plays a fundamental role in the hypersensitive response, but its involvement in other types of PCD, such as that resulting from mechanical stress and natural and cytokinin-induced senescence of cell cultures, has also been demonstrated (Garcês et al., 2001; Carimi et al., 2005). Because of its participation in numerous biotic and abiotic responses, NO has been proposed as a general stress molecule (Gould et al., 2003). However, the mechanisms by which NO determines its effects are far from being completely elucidated, and a number of downstream signaling pathways, involving Ca2+, cyclic GMP, and cyclic ADP-Rib, are involved (Neill et al., 2003; Besson-Bard et al., 2008). NO can also modulate biological responses by direct modification of proteins, reacting with Cys residues (S-nitrosylation), Tyr residues (nitration), or iron and zinc in metalloproteins (metal nitrosylation; Besson-Bard et al., 2008).The aim of this work is to study the plant responses to various concentrations of Cd2+ and, in particular, the role of ROS and NO in the signaling events leading to cell death. Cell cultures of the model plant Arabidopsis were chosen as an experimental system because the homogeneity and undifferentiated state of the cells, combined with the uniform delivery of the treatments, allow a clear and reproducible response. The results point to NO as a master regulator of Cd2+-induced cell death. Possible mechanisms that explain this evidence will be discussed. 相似文献
158.
Laura Dipasquale Agata Gambacorta Rosa Anna Siciliano Maria Fiorella Mazzeo Licia Lama 《Extremophiles : life under extreme conditions》2009,13(2):345-354
This is the first report describing the purification and enzymatic properties of a native invertase (β-D-fructosidase) in
Thermotogales. The invertase of the hydrogen-producing thermophilic bacterium Thermotoga
neapolitana DSM 4359 (hereby named Tni) was a monomer of about 47 kDa having an amino acid sequence quite different from other invertases studied up to now. Its
properties and substrates specificity let us classify this protein as a solute-binding protein with invertase activity. Tni was specific for the fructose moiety and the enzyme released fructose from sucrose and raffinose and the fructose polymer
inulin was hydrolyzed in an endo-type fashion. Tni had an optimum temperature of 85°C at pH 6.0. At temperatures of 80–85°C, the enzyme retained at least 50% of its initial
activity during a 6 h preincubation period. Tni had a K
m
and k
cat
/K
m
values (at 85°C and pH 6.0) of about 14 mM and 5.2 × 108 M−1 s−1, respectively.
Dedicated to the memory of Prof. R. A. Nicolaus, founder of the Institute (1968). 相似文献
159.
Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice
Background
Alzheimer''s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions, extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles within neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role in learning and memory processes and its abnormal regulation might account for cognitive impairments associated with AD.Methodology/Principal Findings
The double transgenic (Tg) CRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein), aged 2 and 6 months, were used to examine in vivo the effects of 5 weeks lithium treatment. BrdU labelling showed a decreased neurogenesis in the subgranular zone of Tg mice compared to non-Tg mice. The decrease of hippocampal neurogenesis was accompanied by behavioural deficits and worsened with age and pathology severity. The differentiation into neurons and maturation of the proliferating cells were also markedly impaired in the Tg mice. Lithium treatment to 2-month-old Tg mice significantly stimulated the proliferation and neuron fate specification of newborn cells and fully counteracted the transgene-induced impairments of cognitive functions. The drug, by the inhibition of GSK-3β and subsequent activation of Wnt/ß-catenin signalling promoted hippocampal neurogenesis. Finally, the data show that the lithium''s ability to stimulate neurogenesis and cognitive functions was lost in the aged Tg mice, thus indicating that the lithium-induced facilitation of neurogenesis and cognitive functions declines as brain Aβ deposition and pathology increases.Conclusions
Lithium, when given on time, stimulates neurogenesis and counteracts AD-like pathology. 相似文献160.
Gianfranco De Feo Simona Signoriello Jane C. Bryce Antonia Del Giudice Giuliana Canzanella Federika Crudele Fiorella Romano Giovanni de Matteis Manuela Florio Fabiano Falasconi Alfonso Savio Pasqualina Giordano Gennaro Daniele Mario Iaccarino Maria Carmela Piccirillo Massimo Di Maio Alessandro Morabito Ciro Gallo Francesco Perrone 《PloS one》2010,5(7)