全文获取类型
收费全文 | 513篇 |
免费 | 41篇 |
出版年
2022年 | 5篇 |
2021年 | 11篇 |
2020年 | 6篇 |
2019年 | 11篇 |
2018年 | 13篇 |
2017年 | 10篇 |
2016年 | 12篇 |
2015年 | 16篇 |
2014年 | 25篇 |
2013年 | 30篇 |
2012年 | 39篇 |
2011年 | 34篇 |
2010年 | 26篇 |
2009年 | 23篇 |
2008年 | 32篇 |
2007年 | 33篇 |
2006年 | 25篇 |
2005年 | 32篇 |
2004年 | 33篇 |
2003年 | 30篇 |
2002年 | 30篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1967年 | 2篇 |
1963年 | 1篇 |
排序方式: 共有554条查询结果,搜索用时 78 毫秒
31.
Sánchez-Sutil MC Gómez-Santos N Moraleda-Muñoz A Martins LO Pérez J Muñoz-Dorado J 《Journal of bacteriology》2007,189(13):4887-4898
Myxococcus xanthus is a soil bacterium that undergoes a unique life cycle among the prokaryotes upon starvation, which includes the formation of macroscopic structures, the fruiting bodies, and the differentiation of vegetative rods into coccoid myxospores. This peculiarity offers the opportunity to study the copper response in this bacterium in two different stages. In fact, M. xanthus vegetative rods exhibit 15-fold-greater resistance against copper than developing cells. However, cells pre-adapted to this metal reach the same levels of resistance during both stages. Analysis of the M. xanthus genome reveals that many of the genes involved in copper resistance are redundant, three of which encode proteins of the multicopper oxidase family (MCO). Each MCO gene exhibits a different expression profile in response to external copper addition. Promoters of cuoA and cuoB respond to Cu(II) ions during growth and development; however, they show a 10-fold-increased copper sensitivity during development. The promoter of cuoC shows copper-independent induction upon starvation, but it is copper up-regulated during growth. Phenotypic analyses of deletion mutants reveal that CuoB is involved in the primary copper-adaptive response; CuoA and CuoC are necessary for the maintenance of copper tolerance; and CuoC is required for normal development. These roles seem to be carried out through cuprous oxidase activity. 相似文献
32.
33.
Aurelio Reyes Laura Melchionda Alessia Nasca Franco Carrara Eleonora Lamantea Alice Zanolini Costanza Lamperti Mingyan Fang Jianguo Zhang Dario Ronchi Sara Bonato Gigliola Fagiolari Maurizio Moggio Daniele Ghezzi Massimo Zeviani 《American journal of human genetics》2015,97(1):186-193
Chronic progressive external ophthalmoplegia (CPEO) is common in mitochondrial disorders and is frequently associated with multiple mtDNA deletions. The onset is typically in adulthood, and affected subjects can also present with general muscle weakness. The underlying genetic defects comprise autosomal-dominant or recessive mutations in several nuclear genes, most of which play a role in mtDNA replication. Next-generation sequencing led to the identification of compound-heterozygous RNASEH1 mutations in two singleton subjects and a homozygous mutation in four siblings. RNASEH1, encoding ribonuclease H1 (RNase H1), is an endonuclease that is present in both the nucleus and mitochondria and digests the RNA component of RNA-DNA hybrids. Unlike mitochondria, the nucleus harbors a second ribonuclease (RNase H2). All affected individuals first presented with CPEO and exercise intolerance in their twenties, and these were followed by muscle weakness, dysphagia, and spino-cerebellar signs with impaired gait coordination, dysmetria, and dysarthria. Ragged-red and cytochrome c oxidase (COX)-negative fibers, together with impaired activity of various mitochondrial respiratory chain complexes, were observed in muscle biopsies of affected subjects. Western blot analysis showed the virtual absence of RNase H1 in total lysate from mutant fibroblasts. By an in vitro assay, we demonstrated that altered RNase H1 has a reduced capability to remove the RNA from RNA-DNA hybrids, confirming their pathogenic role. Given that an increasing amount of evidence indicates the presence of RNA primers during mtDNA replication, this result might also explain the accumulation of mtDNA deletions and underscores the importance of RNase H1 for mtDNA maintenance. 相似文献
34.
Genetic diversification of offspring represents a bet-hedging strategy that evolved as an adaptation to unpredictable environments. The benefits of sexual reproduction come with severe costs. For example, each offspring only carries half of each parent's genetic makeup through direct descent. The lower the reproductive rate, the more substantial the cost when considering the proportion of genes represented in subsequent generations. Positive assortative mating represents a conservative bet-hedging strategy that offsets some of these costs and preserves coadapted genomes in stable and predictable environments, whereas negative assortative mating serves the inverse function of genetic diversification in unstable and unpredictable environments. 相似文献
35.
Exhaustive prediction of physicochemical properties of peptide sequences is used in different areas of biological research. One example is the identification of selective cationic antibacterial peptides (SCAPs), which may be used in the treatment of different diseases. Due to the discrete nature of peptide sequences, the physicochemical properties calculation is considered a high-performance computing problem. A competitive solution for this class of problems is to embed algorithms into dedicated hardware. In the present work we present the adaptation, design and implementation of an algorithm for SCAPs prediction into a Field Programmable Gate Array (FPGA) platform. Four physicochemical properties codes useful in the identification of peptide sequences with potential selective antibacterial activity were implemented into an FPGA board. The speed-up gained in a single-copy implementation was up to 108 times compared with a single Intel processor cycle for cycle. The inherent scalability of our design allows for replication of this code into multiple FPGA cards and consequently improvements in speed are possible. Our results show the first embedded SCAPs prediction solution described and constitutes the grounds to efficiently perform the exhaustive analysis of the sequence-physicochemical properties relationship of peptides. 相似文献
36.
Speed N Saunders C Davis AR Owens WA Matthies HJ Saadat S Kennedy JP Vaughan RA Neve RL Lindsley CW Russo SJ Daws LC Niswender KD Galli A 《PloS one》2011,6(9):e25169
Background
The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address “food-abuse” disorders. We demonstrate a molecular link between impairment of a central kinase (Akt) involved in insulin signaling induced by exposure to a high-fat (HF) diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA) rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT). Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake.Methodology/Principal Findings
We show that consumption of fat-rich food impairs striatal activation of the insulin-activated signaling kinase, Akt. HF-induced Akt impairment, in turn, reduces DAT cell surface expression and function, thereby decreasing DA homeostasis and amphetamine (AMPH)-induced DA efflux. In addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors such as (AMPH)-induced locomotion and increased caloric intake. We restored nigro-striatal Akt phosphorylation using recombinant viral vector expression technology. We observed a rescue of DAT expression in HF fed rats, which was associated with a return of locomotor responses to AMPH and normalization of HF diet-induced hyperphagia.Conclusions/Significance
Acquired disruption of brain insulin action may confer risk for and/or underlie “food-abuse” disorders and the recalcitrance of obesity. This molecular model, thus, explains how even short-term exposure to “the fast food lifestyle” creates a cycle of disordered eating that cements pathological changes in DA signaling leading to weight gain and obesity. 相似文献37.
Aurelio Bairati 《Cell and tissue research》1963,61(5):769-802
Summary The structures formerly described as blood-forming organs or lymph glands in Drosophila melanogaster were re-examined by means of phase contrast, polarized light, and electron microscopy. As a result, the term haemolymph organ is suggested as more appropriate for these peculiar organs. Haemolymph organs of second and third instar larvae, and first stage (white) pupae from a wild strain (Varese) were studied; the methods are described in detail.The haemolymph organ consists of two voluminous anterior lobes and several smaller posterior ones that are ovoid or tubular in shape. The anterior lobes comprise an outer capsule containing some muscle cells, a supporting stroma, and various kinds of cells. The stroma appears to consist of lamellated material of scleroprotein nature similar to that described in other organs of numerous insect species. This material must be considered as a component of the connective tissue characteristic of insect organs.The cells are isolated or organized in groups of various sizes. The following types can be distinguished: rounded cells that are poorly differentiated, polygonal cells with well developed cytoplasm rich in organelles, polygonal cells with clear cytoplasm, and cells that appear to be intermediate form of the types mentioned above.The morphological data presented confirm that the haemolymph organ produces and releases into the haemolymph various types of cells; of these the polygonal cells have a phagocytic and excretory function while only hypotheses can be presented at present concerning the role of the rounded cells. In addition the presence of polygonal cells with clear cytoplasm, showing signs of secretory activity, suggest that the haemolymph organ is involved in the production of substances constituting the fluid fraction of the haemolymph.
Ricerca eseguita con i sussidi del C.N.R. (Impresa Genetica). 相似文献
Ricerca eseguita con i sussidi del C.N.R. (Impresa Genetica). 相似文献
38.
Vicent?Arbona Aurelio J.?Marco Domingo J.?Iglesias María F.?López-Climent Manuel?Talon Aurelio?Gómez-CadenasEmail author 《Plant Growth Regulation》2005,46(2):153-160
In citrus, damage produced by salinity is mostly due to toxic ion accumulation, since this salt-sensitive crop adjusts osmotically with high efficiency. In spite of this observation, the putative role of sugars as osmolites under salinity remains unknown. In this work, we have studied carbohydrate contents (total hexoses, sucrose and starch) in leaves and roots of citrus grown under increasing salinity. The experimental system was characterized through the analyses of several parameters known to be strongly affected by salinity in citrus, such as chloride accumulation, photosynthetic rate, ethylene production and leaf abscission. Three-year-old plants of the Clementina de Nules cultivar grafted on Carrizo citrange rootstock were watered with three different levels of salinity (NaCl was added to the watering solutions to achieve final concentrations of 30, 60 and 90 mM). Data indicate that salt stress caused an accumulation of chloride ions in a way proportional to the external increase in NaCl. The adverse conditions reduced CO2 assimilation, increased ethylene production and triggered abscission of the injured leaves. Data also show that salinity induced progressive depletions of carbohydrates in leaves and roots of citrus plants. This observation clearly indicates that sugar accumulation is not a main component of the osmotic adjustment machinery in citrus. 相似文献
39.
Calabrò C Albanese MP Lauriano ER Martella S Licata A 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2005,43(1):51-56
Histochemical and immunohistochemical study was carried out on nitrinergic innervation and neuroendocrine system in the gill epithelium of the abyssal fish Coelorhynchus coelorhynchus. The results showed that nNOS-positive nerve fibers, originating from the branchial arch were present in the subepithelial tissue of branchial primary filament. nNOS-positive neuroendocrine cells were also present in the primary filaments and secondary lamellae. Numerous mucous cells in the gill epithelium were AB/PAS-positive, while sialic acid was absent as confirmed by neuraminidase reaction and WGA lectin histochemistry. The mucus compounds in abyssal teleost fish are different from those found in pelagic species, being related to their living conditions. In abyssal species, greater numbers of chloride and neuroendocrine cells are involved in the movement of water and electrolytes. Neuroendocrine cells possess oxygen receptors which mediate the cardiovascular and ventilatory response to oxygen deficiency, as reported in teleost species. Besides, NO contributes through nervous stimulation to the regulation of vascular tone and blood circulation in the gill. 相似文献
40.