全文获取类型
收费全文 | 2062篇 |
免费 | 128篇 |
国内免费 | 2篇 |
出版年
2023年 | 10篇 |
2022年 | 9篇 |
2021年 | 34篇 |
2020年 | 22篇 |
2019年 | 41篇 |
2018年 | 44篇 |
2017年 | 38篇 |
2016年 | 63篇 |
2015年 | 99篇 |
2014年 | 107篇 |
2013年 | 140篇 |
2012年 | 169篇 |
2011年 | 166篇 |
2010年 | 97篇 |
2009年 | 92篇 |
2008年 | 132篇 |
2007年 | 121篇 |
2006年 | 114篇 |
2005年 | 100篇 |
2004年 | 108篇 |
2003年 | 92篇 |
2002年 | 95篇 |
2001年 | 19篇 |
2000年 | 12篇 |
1999年 | 18篇 |
1998年 | 10篇 |
1997年 | 18篇 |
1996年 | 10篇 |
1995年 | 8篇 |
1994年 | 13篇 |
1993年 | 14篇 |
1992年 | 16篇 |
1991年 | 5篇 |
1990年 | 15篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 9篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1969年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有2192条查询结果,搜索用时 15 毫秒
1.
Marika Cordaro Irene Paterniti Rosalba Siracusa Daniela Impellizzeri Emanuela Esposito Salvatore Cuzzocrea 《Molecular neurobiology》2017,54(4):2415-2427
Autophagy is an intracellular catabolic mechanism for the degradation of cytoplasmic constituents in the autophagosomal–lysosomal pathway. This mechanism plays an important role in homeostasis and it is defective in certain diseases. Preceding studies have revealed that autophagy is developing as an important moderator of pathological responses associated to spinal cord injury (SCI) and plays a crucial role in secondary injury initiating a progressive degeneration of the spinal cord. Thus, based on this evidence in this study, we used two different selective inhibitors of mTOR activity to explore the functional role of autophagy in an in vivo model of SCI as well as to determine whether the autophagic process is involved in spinal cord tissue damage. We treated animals with a novel synthetic inhibitor temsirolimus and with a dual mTORC1 and mTORC2 inhibitor KU0063794 matched all with the well-known inhibitor of mTOR the rapamycin. Our results demonstrated that mTOR inhibitors could regulate the neuroinflammation associated to SCI and the results that we obtained evidently demonstrated that rapamycin and temsirolimus significantly diminished the expression of iNOS, COX2, GFAP, and re-established nNOS levels, but the administration of KU0063794 is able to blunt the neuroinflammation better than rapamycin and temsirolimus. In addition, neuronal loss and cell mortality in the spinal cord after injury were considerably reduced in the KU0063794-treated mice. Accordingly, taken together our results denote that the administration of KU0063794 produced a neuroprotective function at the lesion site following SCI, representing a novel therapeutic approach after SCI. 相似文献
2.
Gianfranco Sebastio Ornella Castiglione Barbara Incerti Donatello Salvatore Francesca Santamaria 《Human genetics》1990,85(4):430-431
Summary Fifty one independent cystic fibrosis (CF) families originating from a restricted area of Southern Italy (Campania) have been
analyzed for KM19 and XV2c haplotypes and the ΔF508 mutation: 54% of the total CF chromosomes show the ΔF508 mutation. No
significative correlations were obtained when clinical score, radiological score,Pseudomonas colonization, or clinical symptoms at presentation were matched with the presence or absence of the ΔF508 mutation. 相似文献
3.
Salvatore Chiantia Grzegorz Chwastek Zaiguo Li Petra Schwille 《生物化学与生物物理学报:生物膜》2008,1778(5):1356-1364
Ceramide-induced alterations in the lateral organization of membrane proteins can be involved in several biological contexts, ranging from apoptosis to viral infections. In order to investigate such alterations in a simple model, we used a combined approach of atomic force microscopy, scanning fluorescence correlation spectroscopy and confocal fluorescence imaging to study the partitioning of different membrane components in sphingomyelin/dioleoyl-phosphatidylcholine/cholesterol/ceramide supported bilayers. Such model membranes exhibit coexistence of liquid-disordered, liquid-ordered (raft-like) and ceramide-rich lipid phases. Our results show that components with poor affinity toward the liquid-ordered phase, such as several fluorescent lipid analogues or the synaptic protein Synaptobrevin 2, are excluded from ceramide-rich domains. Conversely, we show for the first time that the raft-associated protein placental alkaline phosphatase (GPI-PLAP) and the ganglioside GM1 are enriched in such domains, while exhibiting a strong decrease in lateral diffusion. Analogue modulation of the local concentration and dynamics of membrane proteins/receptors by ceramide can be of crucial importance for the biological functions of cell membranes. 相似文献
4.
5.
Silene ichnusae (Caryophyllaceae) a new species of S. sect. Siphonomoipha is described and illustrated. It is a rare chasmophyte localized at Capo Falcone (W Sardinia), on siliceous rocks near the sea. Its relationships with S. velutina, of the S. mollissima group, are discussed. 相似文献
6.
7.
Vertical ionization energies (VIEs) of medazepam, nordazepam and their molecular subunits have been calculated using the electron
propagator method in the P3/CEP-31G* approximation. Vertical electron affinities (VEAs) have been obtained with a ∆SCF procedure
at the DFT-B3LYP/6-31+G* level of theory. Excellent correlations have been achieved between IEcalc and IEexp, allowing reliable assignment of the ionization processes. Our proposed assignment differs in many instances from that previously
reported in the literature. The electronic structure of the frontier Dyson orbitals shows that the IE and EA values of the
benzodiazepines can be modulated by substitution at the benzene rings. Hardness values, evaluated as (IE − EA)/2, follow the
trend of the experimental singlet transition energies. Medazepam is a less hard (i.e., less stable) compound than nordazepam. 相似文献
8.
Giuliano Bonanomi Guido Incerti Gaspare Cesarano Salvatore A. Gaglione Virginia Lanzotti 《PloS one》2015,10(1)
Cigarette butts (CBs) are the most common type of litter on earth, with an estimated 4.5 trillion discarded annually. Apart from being unsightly, CBs pose a serious threat to living organisms and ecosystem health when discarded in the environment because they are toxic to microbes, insects, fish and mammals. In spite of the CB toxic hazard, no studies have addressed the effects of environmental conditions on CB decomposition rate. In this study we investigate the interactive effects of substrate fertility and N transfer dynamics on CB decomposition rate and carbon quality changes. We carried out an experiment using smoked CBs and wood sticks, used as a slow decomposing standard organic substrate, incubated in both laboratory and field conditions for two years. CB carbon quality changes during decomposition was assessed by 13C CPMAS NMR. Our experiment confirmed the low degradation rate of CBs which, on average, lost only 37.8% of their initial mass after two years of decomposition. Although a net N transfer occurred from soil to CBs, contrary to our hypothesis, mass loss in the medium-term (two years) was unaffected by N availability in the surrounding substrate. The opposite held for wood sticks, in agreement with the model that N-rich substrates promote the decomposition of other N-poor natural organic materials with a high C/N ratio. As regards CB chemical quality, after two years of decomposition 13C NMR spectroscopy highlighted very small changes in C quality that are likely to reflect a limited microbial attack. 相似文献
9.
Carla Carluccio Francesco Salvatore Arianna Fornili 《Journal of biomolecular structure & dynamics》2016,34(3):497-507
The enzyme phenylalanine hydroxylase (PAH) is defective in the inherited disorder phenylketonuria. PAH, a tetrameric enzyme, is highly regulated and displays positive cooperativity for its substrate, Phe. Whether Phe binds to an allosteric site is a matter of debate, despite several studies worldwide. To address this issue, we generated a dimeric model for Phe–PAH interactions, by performing molecular docking combined with molecular dynamics simulations on human and rat wild-type sequences and also on a human G46S mutant. Our results suggest that the allosteric Phe-binding site lies at the dimeric interface between the regulatory and the catalytic domains of two adjacent subunits. The structural and dynamical features of the site were characterized in depth and described. Interestingly, our findings provide evidence for lower allosteric Phe-binding ability of the G46S mutant than the human wild-type enzyme. This also explains the disease-causing nature of this mutant. 相似文献
10.
Angela Avenoso Angela D'Ascola Michele Scuruchi Giuseppe Mandraffino Salvatore Campo Giuseppe M. Campo 《Biochimica et Biophysica Acta (BBA)/General Subjects》2021,1865(1):129731
BackgroundSmall HA fragments are produced during cartilage degradation and their role seems to be preponderant during pathologies in which cartilage injury contribute to trigger and perpetuate the inflammatory mechanism.Several reports have increasingly shown that MicroRNAs (miRs), a small non-coding mRNAs are involved in the regulation of multiple biological processes, including cell proliferation and inflammation response in different pathologies, among them miR146a seems to be involved in inflammatory processes.MethodsStarting by these evidences we investigated the levels of miR146a and its correlation with inflammatory mediators in an experimental model of 6-mer HA-induced inflammatory response in human cultured chondrocytes.ResultsTreatment of chondrocytes with 6-mer HA showed up-regulation in inflammation parameters such as TLR-4, and CD44 receptors activation, IL-6, IL-1β and MMP-13 mRNA expression and proteins production, as well as NF-kB activation. We also revealed an up-regulation of miR146a. Transfection with a miR146a mimic or miR146a inhibitor produced the following effects: chondrocytes receiving miR146a mimic and then 6-mer HA significantly reduced inflammatory cytokines and MMP-13, while exposition of chondrocytes with miR146a inhibitor and then the 6-mer HA incremented the activity of damaging cytokines and MMP13. Expression of CD44 receptor was not affected by miR-146a treatments, while TLR-4 expression and NF-kB activation were modified.ConclusionsWe concluded that up-regulation of miR146a occurred in 6-mer HA-induced inflammation response may reduce the inflammatory cascade by modulating TLR-4 and NF-kB activation.General significanceThese results could be useful in develop new therapeutic strategies with the aim to reduce OA and RA incidence. 相似文献