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21.
Ylenia Ingrasciotta Janet Sultana Francesco Giorgianni Andrea Fontana Antonio Santangelo Daniele Ugo Tari Domenico Santoro Vincenzo Arcoraci Margherita Perrotta Luisa Ibanez Gianluca Trifirò 《PloS one》2015,10(4)
Background
Non-steroidal anti-inflammatory agents (NSAIDs) are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD), specifically, across various NSAIDs.Aim
The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.Methods
A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID). Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID), with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.Results
Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44) and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44), meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87) and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21).Conclusions
The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam. 相似文献22.
Sara Mandelli Emma Riva Mauro Tettamanti Paolo Detoma Adriano Giacomin Ugo Lucca 《PloS one》2015,10(8)
Background
Kidney function declines considerably with age, but little is known about its clinical significance in the oldest-old.Objectives
To study the association between reduced glomerular filtration rate (GFR) estimated according to five equations with mortality in the oldest-old.Design
Prospective population-based study.Setting
Municipality of Biella, Piedmont, Italy.Participants
700 subjects aged 85 and older participating in the “Health and Anemia” Study in 2007–2008.Measurements
GFR was estimated using five creatinine-based equations: the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD), MAYO Clinic, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study-1 (BIS-1). Survival analysis was used to study mortality in subjects with reduced eGFR (<60 mL/min/1.73m2) compared to subjects with eGFR ≥60 mL/min/1.73m2.Results
Prevalence of reduced GFR was 90.7% with the C-G, 48.1% with MDRD, 23.3% with MAYO, 53.6% with CKD-EPI and 84.4% with BIS-1. After adjustment for confounders, two-year mortality was significantly increased in subjects with reduced eGFR using BIS-1 and C-G equations (adjusted HRs: 2.88 and 3.30, respectively). Five-year mortality was significantly increased in subjects with eGFR <60 mL/min/1.73m2 using MAYO, CKD-EPI and, in a graduated fashion in reduced eGFR categories, MDRD. After 5 years, oldest old with an eGFR <30 mL/min/1.73m2 showed a significantly higher risk of death whichever equation was used (adjusted HRs between 2.04 and 2.70).Conclusion
In the oldest old, prevalence of reduced eGFR varies noticeably depending on the equation used. In this population, risk of mortality was significantly higher for reduced GFR estimated with the BIS-1 and C-G equations over the short term. Though after five years the MDRD appeared on the whole a more consistent predictor, differences in mortality prediction among equations over the long term were less apparent. Noteworthy, subjects with a severely reduced GFR were consistently at higher risk of death regardless of the equation used to estimate GFR. 相似文献23.
Massimiliano Biagini Manuela Garibaldi Susanna Aprea Alfredo Pezzicoli Francesco Doro Marco Becherelli Anna Rita Taddei Chiara Tani Simona Tavarini Marirosa Mora Giuseppe Teti Ugo D'Oro Sandra Nuti Marco Soriani Immaculada Margarit Rino Rappuoli Guido Grandi Nathalie Norais 《Molecular & cellular proteomics : MCP》2015,14(8):2138-2149
Bacterial lipoproteins are attractive vaccine candidates because they represent a major class of cell surface-exposed proteins in many bacteria and are considered as potential pathogen-associated molecular patterns sensed by Toll-like receptors with built-in adjuvanticity. Although Gram-negative lipoproteins have been extensively characterized, little is known about Gram-positive lipoproteins. We isolated from Streptococcus pyogenes a large amount of lipoproteins organized in vesicles. These vesicles were obtained by weakening the bacterial cell wall with a sublethal concentration of penicillin. Lipid and proteomic analysis of the vesicles revealed that they were enriched in phosphatidylglycerol and almost exclusively composed of lipoproteins. In association with lipoproteins, a few hypothetical proteins, penicillin-binding proteins, and several members of the ExPortal, a membrane microdomain responsible for the maturation of secreted proteins, were identified. The typical lipidic moiety was apparently not necessary for lipoprotein insertion in the vesicle bilayer because they were also recovered from the isogenic diacylglyceryl transferase deletion mutant. The vesicles were not able to activate specific Toll-like receptor 2, indicating that lipoproteins organized in these vesicular structures do not act as pathogen-associated molecular patterns. In light of these findings, we propose to name these new structures Lipoprotein-rich Membrane Vesicles.Bacterial lipoproteins (Lpps)1 are a subset of membrane proteins that are covalently modified with a lipidic moiety at their N-terminal cysteine residue. It is commonly reported that Lpps of Gram-positive bacteria are processed by two key enzymes; the prolipoprotein diacylglyceryl transferase (Lgt) and the lipoprotein signal peptidase (Lsp). The Lgt enzyme recognizes a so-called lipobox motif in the C-terminal region of the signal peptide of a premature lipoprotein and transfers a diacylglyceryl moiety to the cysteine residue of the lipobox (1), (2). Subsequently, the Lsp enzyme cleaves the signal peptide resulting in a mature Lpp (3), (4). Nevertheless, recent reports have suggested that N-acylation occurs in bacteria that lack the Gram-negative homologous apolipoprotein N-acyltransferase (Lnt) gene responsible for this modification (5, 6), and that Lpp N-terminal could also be modified with an acetyl group in some Gram-positive (7).Lpps have been described as virulence factors because they play critical roles in membrane stabilization, nutrient uptake, antibiotic resistance, bacterial adhesion to host cells, protein maturation and secretion and many of them still have unknown function (8). Several studies have suggested that bacterial Lpps are pathogen-associated molecular patterns (PAMPs) sensed by the mammalian host through Toll-like receptor 2 (TLR2) heterodimerized with TLR1 or TLR6 to induce innate immunity activation and to control adaptive immunity (9–12). TLR2 plays a critical role in the host response to the Gram-positive bacteria Staphylococcus aureus (13) and Streptococcus agalactiae (14). Although TLR2 has been considered a receptor for various structurally unrelated PAMPs, recent studies have suggested that, via their lipid moiety, bacterial Lpps function as the major, if not the sole, ligand molecules responsible for TLR2 activation (15). Although Gram-negative Lpps have been widely studied, little information is available for Gram-positive Lpps (16) and the ways they are released into the bacterial extracellular compartment and reach the host immune system remain unclear.We focused our attention on Lpps release by Streptococcus pyogenes. This Gram-positive bacterium is an important human pathogen that causes a wide range of diseases from superficial and self-limiting infection, e.g. pharyngitis and impetigo, to more systemic or invasive diseases like necrotizing fasciitis and septicemia (17). Understanding the role of bacterial Lpps in mediating innate and acquired immunity can be instrumental for the therapy and prophylaxis of human S. pyogenes infections. In this study, we showed that in S. pyogenes Lpps are released into the growth medium within vesicle-like structures in minute amounts. Conditions weakening the bacterial cell wall, such as the addition of sublethal concentrations of penicillin to the bacterial growth medium enhanced this phenomenon and allowed the recovery of sufficient material to enable an in-depth characterization. Proteomic analysis of the vesicles revealed that they were almost exclusively constituted of Lpps. A total of 28 Lpps were identified, representing more than 72% of the Lpps predicted from the genome of the strain under investigation. In addition, multiple transmembrane domain proteins were not found in abundance associated to the vesicles, indicating that vesicles were not representative of the bacterial membrane. We defined these vesicles as Lipoprotein-rich Membrane Vesicles (LMVs).Common characteristics are shared between the LMVs and the ExPortal described for the first time by Rosch and Caparon (18). This asymmetric and distinct membrane microdomain has been reported to be enriched in anionic phospholipids and acts in promoting the biogenesis of secreted proteins by coordinating interactions between nascent unfolded secretory proteins and the accessory factors required for their maturation (19–21). An association between ExPortal and peptidoglycan synthesis has also been reported (22). Similarly, LMVs are enriched in anionic phosphatidylglycerol, enzymes involved in protein maturation/secretion and cell wall biogenesis, suggesting that LMVs might derive from the ExPortal. Finally, we showed that LMVs do not induce TLR2 activation, indicating that the Lpps did not act as PAMPs when integrated into the LMVs. 相似文献
24.
Gianluigi Forloni Mauro Tettamanti Ugo Lucca Yasmin Albanese Elena Quaglio Roberto Chiesa Alessandra Erbetta Flavio Villani Veronica Redaelli Fabrizio Tagliavini Vladimiro Artuso Ignazio Roiter 《朊病毒》2015,9(2):75-79
The text describes a preventive clinical trial with drug treatment in a very rare neurodegenerative disease (Fatal familial Insomnia, FFI) designed with the help of individuals at genetic risk of developing the disease, asymptomatic carriers, who have agreed to be exposed over a 10-year period to doxycycline, an antibiotic with anti-prion activity. At least 10 carriers of the FFI mutation over 42 y old will be treated with doxycycline (100 mg/die) and the incidence of the disease will be compared to that of an historical dataset. For ethical reasons a randomized, double-blind, placebo-controlled trial was not feasible, however the study design and the statistical analysis ensure the scientific value of the results. This approach might represent an important breakthrough in terms of potential therapy and knowledge of rare diseases that could give some hopes to these neglected patients. 相似文献
25.
Temporal constraints on the potential role of fry odors as cues of past reproductive success for spawning lake trout 下载免费PDF全文
Tyler J. Buchinger J. Ellen Marsden Thomas R. Binder Mar Huertas Ugo Bussy Ke Li James E. Hanson Charles C. Krueger Weiming Li Nicholas S. Johnson 《Ecology and evolution》2017,7(23):10196-10206
Deciding where to reproduce is a major challenge for most animals. Many select habitats based upon cues of successful reproduction by conspecifics, such as the presence of offspring from past reproductive events. For example, some fishes select spawning habitat following odors released by juveniles whose rearing habitat overlaps with spawning habitat. However, juveniles may emigrate before adults begin to search for spawning habitat; hence, the efficacy of juvenile cues could be constrained by degradation or dissipation rates. In lake trout (Salvelinus namaycush), odors deposited by the previous year's offspring have been hypothesized to guide adults to spawning reefs. However, in most extant populations, lake trout fry emigrate from spawning reefs during the spring and adults spawn during the fall. Therefore, we postulated that the role of fry odors in guiding habitat selection might be constrained by the time between fry emigration and adult spawning. Time course chemical, physiological, and behavioral assays indicated that the odors deposited by fry likely degrade or dissipate before adults select spawning habitats. Furthermore, fry feces did not attract wild lake trout to constructed spawning reefs in Lake Huron. Taken together, our results indicate fry odors are unlikely to act as cues for lake trout searching for spawning reefs in populations whose juveniles emigrate before the spawning season, and underscore the importance of environmental constraints on social cues. 相似文献
26.
Raimondi S Roncaglia L De Lucia M Amaretti A Leonardi A Pagnoni UM Rossi M 《Applied microbiology and biotechnology》2009,81(5):943-950
Twenty-two strains of Bifidobacterium, representative of eight major species of human origin, were screened for their ability to transform the isoflavones daidzin
and daidzein. Most of the strains released the aglycone from daidzin and 12 gave yields higher than 90%. The kinetics of growth,
daidzin consumption, and daidzein production indicated that the hydrolytic activity occurred during the growth. The supernatant
of the majority of the strains did not release the aglycone from daidzin, suggesting that cell-associated β-glucosidases (β-Glu)
are mainly responsible for the metabolism of soybean glyco-conjugates. Cell-associated β-Glu was mainly intracellular and
significantly varied among the species and the strains. The lack of β-Glu was correlated with the inability to hydrolyze daidzin.
Although S-equol production by anaerobic intestinal bacteria has been established, information on S-equol-producing bifidobacteria
is contradictory. In this study, 22 bifidobacteria failed to transform daidzein into reduced metabolites under all the experimental
conditions, excluding any role in the reductive pathway of daidzein toward the production of S-equol. These results suggest
that selected probiotic strains of Bifidobacterium can be used to speed up the release of daidzein, improving its bioavailability for absorption by colonic mucosa and/or biotransformation
to S-equol by other intestinal microorganisms. 相似文献
27.
Franco Bellesia Romano Grandi Alessandro Marchesini Ugo M. Pagnoni Roberto Trave 《Phytochemistry》1975,14(8):1737-1740
Ageratriol is biosynthesized from agerol through a diepoxide derivative. Mevalonic acid incorporation revealed that the formation of the isopropenylic double bond is not stereospecific. 相似文献
28.
Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway 总被引:7,自引:0,他引:7
Seternes OM Mikalsen T Johansen B Michaelsen E Armstrong CG Morrice NA Turgeon B Meloche S Moens U Keyse SM 《The EMBO journal》2004,23(24):4780-4791
Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK), which is regulated by protein stability. However, its function is unknown and no physiological substrates for ERK3 have yet been identified. Here we demonstrate a specific interaction between ERK3 and MAPK-activated protein kinase-5 (MK5). Binding results in nuclear exclusion of both ERK3 and MK5 and is accompanied by ERK3-dependent phosphorylation and activation of MK5 in vitro and in vivo. Endogenous MK5 activity is significantly reduced by siRNA-mediated knockdown of ERK3 and also in fibroblasts derived from ERK3-/- mice. Furthermore, increased levels of ERK3 protein detected during nerve growth factor-induced differentiation of PC12 cells are accompanied by an increase in MK5 activity. Conversely, MK5 depletion causes a dramatic reduction in endogenous ERK3 levels. Our data identify the first physiological protein substrate for ERK3 and suggest a functional link between these kinases in which MK5 is a downstream target of ERK3, while MK5 acts as a chaperone for ERK3. Our findings provide valuable tools to further dissect the regulation and biological roles of both ERK3 and MK5. 相似文献
29.
30.
Kinetics during stair ambulation is currently studied via either the use of sensing elements embedded in the steps of the stairway or simple rigid blocks of different height positioned on top of existing force platforms, typically embedded in a walkway for gait analysis. Neither of these approaches is truly satisfactory for gait analysis laboratories. The first one is expensive and requires setting up a dedicated space. The second approach is limited by the number of platforms utilized in the laboratory for evaluating level walking. This communication proposes a novel design, referred to as "interlaced stairway", that allows one to measure ground reaction force and position of the center of pressure (CoP) for four foot contacts during stair ambulation using only two force platforms embedded in a walkway. Accuracy and precision of the CoP estimates and natural frequency of the stairway structure were derived from experimental data. Test results indicate that the interlaced stairway structure does not appreciably reduce the quality of the measures gathered by the existing force platforms. Specifically, the estimated CoP coordinates show good agreement with the horizontal coordinates of the geometric center of the calibration object utilized to assess accuracy and precision of the CoP estimates (max difference < 6 mm). The natural frequency of the stairway structure is lower than the one for the unloaded force platform but higher than the frequency components of interest in stair ambulation analysis. 相似文献