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131.
Valli De Re Laura Caggiari Mariangela De Zorzi Ombretta Repetto Anna Linda Zignego Francesco Izzo Maria Lina Tornesello Franco Maria Buonaguro Alessandra Mangia Domenico Sansonno Vito Racanelli Salvatore De Vita Pietro Pioltelli Emanuela Vaccher Massimiliano Beretta Cesare Mazzaro Massimo Libra Andrea Gini Antonella Zucchetto Renato Cannizzaro Paolo De Paoli 《PloS one》2015,10(5)
132.
Alexander B. Taylor Livia Pica-Mattoccia Chiara M. Polcaro Enrica Donati Xiaohang Cao Annalisa Basso Alessandra Guidi Anastasia R. Rugel Stephen P. Holloway Timothy J. C. Anderson P. John Hart Donato Cioli Philip T. LoVerde 《PLoS neglected tropical diseases》2015,9(10)
Background
For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. m ansoni sulfotransferase (SmSULT) was identified as the target of OXA action.Methodology/Principal Findings
Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, while R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA.Conclusions/Significance
Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. These findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds. 相似文献133.
Enrica Olivola Mariangela Pierantozzi Paola Imbriani Claudio Liguori Mario Stampanoni Bassi Marco Conti Vincenza D′Angelo Nicola Biagio Mercuri Alessandro Stefani 《PloS one》2014,9(7)
In Parkinson''s disease (PD), several studies have detected an impaired serotonin (5-HT) pathway, likely affecting both motor and non-motor domains. However, the precise impact of 5-HT impairment is far from established. Here, we have used a HPLC chromatographic method, in a homogenous cohort (n = 35) of non fluctuating, non dyskinetic PD patients, to assess the concentration of 5-HT and its metabolite 5-HIAA in peripheral cerebrospinal fluid (CSF) obtained from lumbar puncture (LP). LP was performed following three days of therapy withdrawal, in order to vanish the effects of prolonged released dopamine agonists (DA), and in absence of any serotonergic agent. The PD patient group showed a significantly reduced CSF level of both 5-HT and 5-HIAA compared to either age-matched control subjects (n = 18), or Alzheimer''s disease patients (n = 20). However, no correlation emerged between 5-HT/5-HIAA concentrations and UPDRS-III (r = −0.12), disease duration (r = −0.1), age (r = −0.27) and MMSE (r = 0.11). Intriguingly, low CSF 5-HT levels did not differ for gender or for motor phenotype (in terms of non-tremor dominant subtype and tremor dominant subtype). Further, low CSF 5-HT levels did not correlate with the presence of depression, apathy or sleep disturbance. Our findings support the contention that 5-HT impairment is a cardinal feature of stable PD, probably representing a hallmark of diffuse Lewy bodies deposition in the brainstem. However, clinical relevance remains uncertain. Given these findings, an add-on therapy with serotonergic agents seems questionable in PD patients, or should be individually tailored, unless severe depression is present. 相似文献
134.
Eugenio Galano Erika Mangiapane Juliusz Bianga Angelo Palmese Enrica Pessione Joanna Szpunar Ryszard Lobinski Angela Amoresano 《Molecular & cellular proteomics : MCP》2013,12(8):2196-2204
An analytical approach was developed to study the incorporation of selenium (Se), an important trace element involved in the protection of cells from oxidative stress, into the well-known probiotic Lactobacillus reuteri Lb2 BM-DSM 16143. The analyses revealed that about half of the internalized Se was covalently incorporated into soluble proteins. Se-enriched proteins were detected in 2D gels by laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP MSI) and identified by capillary HPLC with the parallel ICP MS (78Se) and electrospray Orbitrap MS/MS detection. On the basis of the identification of 10 richest in selenium proteins, it was demonstrated that selenium was incorporated by the strain exclusively as selenocysteine. Also, the exact location of selenocysteine within the primary sequence was determined. This finding is in a striking contrast to another common nutraceutical, Se-enriched yeast, which incorporates Se principally as selenomethionine.In recent years selenium (Se)1 has received considerable attention as an essential element for human health. Severe Se deficiency is linked to oxidative stress and aging (1), elevated mortality with HIV (2), and irreversible brain injury (seizures, Parkinson''s disease) (3). Se occurs in nature principally in four inorganic chemical forms: the highly toxic selenide (Se2−−) (4), the moderately toxic selenate (SeO42−−) and selenite (SeO32−−), and elemental selenium (Se0) which is essentially nontoxic and can be stored by several bacterial species as nanoparticles on the cell surface (5, 6, 7). Inorganic selenium can be converted by biological systems (microorganisms, plants, and mammals) into seleno-amino acids, which are then incorporated into proteins. The two most common seleno-amino acids are selenomethionine (SeMet) and selenocysteine (SeCys). The former is synthesized via a route similar to the sulfur metabolic pathway in which selenium substitutes sulfur with no alteration of the protein structure (8, 9). The insertion of SeCys is genetically encoded by the UGA (TGA) codon and requires a SECIS element downstream of such a codon, a specific tRNA[Ser]Sec and accessory proteins (10).Selenoproteins containing genetically encoded SeCys are known to be synthesized by several bacteria. Among Gram-negative ones, E. coli produces three forms of selenated formate dehydrogenase (FdhN, FdhO, FdhH) (11). Among Gram-positive bacteria, all the selenoproteins experimentally known were found exclusively in anaerobic bacteria belonging to the clostridial clade. Examples include glycine reductase from Clostridium sticklandii (12) and Eubacterium acidaminophilum (13), proline reductase in C. sticklandii (14), xanthine dehydrogenase in C. acidiurici (15), and several antioxidant defense proteins (16). Enterococcus faecalis is the only member of the Firmicutes/Lactobacillales subdivision containing a SeCys-decoding trait (SelD) (17).Lactobacillus reuteri species has been widely described as a probiotic: it produces antimicrobial compounds, such as reuterin, with a broad spectrum of action (18), it is effective against diarrhea in children (19) and possesses immunomodulatory (potent TNF-inhibitory activity) effects in humans (20). Because L. reuteri species are native inhabitants of human microbiota, the association of the probiotic feature L. reuteri Lb2 BM-DSM 16143 with its ability to fix selenium into proteins, offers an innovative approach to combat human selenium deficiency.The objectives of this study were to investigate the ability of Firmicutes/Lactobacillales subdivision, Lactobacillus reuteri Lb2 BM-DSM 16143to incorporate selenium into proteins, and to investigate, for the first time, its speciation in order to identify the pathway(s) of this process (SeMet or SeCys). For this purpose an analytical approach based on laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP MSI) of Se-containing proteins in 2D gel electrophoresis, followed by their identification by capillary HPLC - electrospray Orbitrap MS/MS assisted by the quantitative control of selenium elution by ICP MS, was developed. 相似文献
135.
Beltrame L Calura E Popovici RR Rizzetto L Guedez DR Donato M Romualdi C Draghici S Cavalieri D 《Bioinformatics (Oxford, England)》2011,27(15):2127-2133
MOTIVATION: Many models and analysis of signaling pathways have been proposed. However, neither of them takes into account that a biological pathway is not a fixed system, but instead it depends on the organism, tissue and cell type as well as on physiological, pathological and experimental conditions. RESULTS: The Biological Connection Markup Language (BCML) is a format to describe, annotate and visualize pathways. BCML is able to store multiple information, permitting a selective view of the pathway as it exists and/or behave in specific organisms, tissues and cells. Furthermore, BCML can be automatically converted into data formats suitable for analysis and into a fully SBGN-compliant graphical representation, making it an important tool that can be used by both computational biologists and 'wet lab' scientists. Availability and implementation: The XML schema and the BCML software suite are freely available under the LGPL for download at http://bcml.dc-atlas.net. They are implemented in Java and supported on MS Windows, Linux and OS X. 相似文献
136.
137.
Mazzoli R Fattori P Lamberti C Giuffrida MG Zapponi M Giunta C Pessione E 《Molecular bioSystems》2011,7(3):598-607
In the present study, the high isoelectric point sub-proteome of Acinetobacter radioresistens S13 grown on aromatic compounds (benzoate or phenol) was analyzed and compared to the protein pattern, in the same pI range, of acetate-grown bacteria (control condition). Analyses concerned both soluble and membrane enriched proteomes and led to the identification of 25 proteins that were differentially expressed among the growth conditions considered: most of them were up-regulated in cells grown on aromatic compounds. Up to 17 identified proteins can be, more or less directly, related to the so called "envelope stress responses": these signal transduction pathways are activated when bacterial cells are exposed to stressing environments (e.g., heat, pH stress, organic solvents, osmotic stress) causing accumulation of misfolded/unfolded cell wall proteins into the periplasmic space. For, at least, five of these proteins (a DegP-like serine protease, a peptidyl-prolyl cis-trans isomerase, a phosphatidylserine decarboxylase, a pseudouridine synthase, and a TolB-like protein) a direct induction via either the σ(E) or the Cpx alternative signalling systems mediating envelope stress responses was previously demonstrated in Gram-negative bacteria. The proteins identified in this study include periplasmic proteases, chaperones, enzymes catalyzing peptydoglycan biogenesis, proteins involved in outer membrane integrity, cell surface properties and cellular redox homeostasis. The present study brings additional information to previous works on the acidic proteome of A. radioresistens S13, thus complementing and refining the metabolic picture of this bacterial strain during growth on aromatic compounds. 相似文献
138.
Melatonin modulates many important functions within the eye by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylate cyclase. In the mouse, Melatonin Receptors type 1 (MT(1)) mRNAs have been localized to photoreceptors, inner retinal neurons, and ganglion cells, thus suggesting that MT(1) receptors may play an important role in retinal physiology. Indeed, we have recently reported that absence of the MT(1) receptors has a dramatic effect on the regulation of the daily rhythm in visual processing, and on retinal cell viability during aging. We have also shown that removal of MT(1) receptors leads to a small (3-4 mmHg) increase in the level of the intraocular pressure during the night and to a significant loss (25-30%) in the number of cells within the retinal ganglion cell layer during aging. In the present study we investigated the cellular distribution in the C3H/f(+/+) mouse retina of MT(1) receptors using a newly developed MT(1) receptor antibody, and then we determined the role that MT(1) signaling plays in the circadian regulation of the mouse electroretinogram, and in the retinal dopaminergic system. Our data indicate that MT(1) receptor immunoreactivity is present in many retinal cell types, and in particular, on rod and cone photoreceptors and on intrinsically photosensitive ganglion cells (ipRGCs). MT(1) signaling is necessary for the circadian rhythm in the photopic ERG, but not for the circadian rhythm in the retinal dopaminergic system. Finally our data suggest that the circadian regulation of dopamine turnover does not drive the photopic ERG rhythm. 相似文献
139.
Holterhues J Bordignon E Klose D Rickert C Klare JP Martell S Li L Engelhard M Steinhoff HJ 《Biophysical journal》2011,(9):2275-2282
Sensory rhodopsin II (NpSRII) is a phototaxis receptor of Natronomonas pharaonis that performs its function in complex with its cognate transducer (NpHtrII). Upon light activation NpSRII triggers by means of NpHtrII a signal transduction chain homologous to the two component system in eubacterial chemotaxis. The D75N mutant of NpSRII, which lacks the blue-shifted M intermediate and therefore exhibits a significantly faster photocycle compared to the wild-type, mediates normal phototaxis responses demonstrating that deprotonation of the Schiff base is not a prerequisite for transducer activation. Using site-directed spin labeling and time resolved electron paramagnetic-resonance spectroscopy, we show that the mechanism revealed for activation of the wild-type complex, namely an outward tilt motion of the cytoplasmic part of the receptor helix F and a concomitant rotation of the transmembrane transducer helix TM2, is also valid for the D75N variant. Apparently, the D75N mutation shifts the ground state conformation of NpSRII-D75N and its cognate transducer into the direction of the signaling state. 相似文献
140.
Simona Cammarota Lucio Marcello Falconio Dario Bruzzese Alberico Luigi Catapano Manuela Casula Anna Citarella Luigi De Luca Maria Elena Flacco Lamberto Manzoli Maria Masulli Enrica Menditto Andrea Mezzetti Salvatore Riegler Ettore Novellino Gabriele Riccardi 《PloS one》2013,8(11)