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81.
NA-Seq: A Discovery Tool for the Analysis of Chromatin Structure and Dynamics during Differentiation
Gaetano Gargiulo Samuel Levy Gabriele Bucci Mauro Romanenghi Lorenzo Fornasari Karen Y. Beeson Susanne M. Goldberg Matteo Cesaroni Marco Ballarini Fabio Santoro Natalie Bezman Gianmaria Frigè Philip D. Gregory Michael C. Holmes Robert L. Strausberg Pier Giuseppe Pelicci Fyodor D. Urnov Saverio Minucci 《Developmental cell》2009,16(3):466-481
82.
Antonella Santoro Anna Rita CappelloMarianna Madeo Emanuela MartelloDomenico Iacopetta Vincenza Dolce 《Biochimica et Biophysica Acta (BBA)/General Subjects》2011
Background
Fosfomycin is widely used to treat urinary tract and pediatric gastrointestinal infections of bacteria. It is supposed that this antibiotic enters cells via two transport systems, including the bacterial Glycerol-3-phosphate Transporter (GlpT). Impaired function of GlpT is one mechanism for fosfomycin resistance.Methods
The interaction of fosfomycin with the recombinant and purified GlpT of Escherichia coli reconstituted in liposomes has been studied. IC50 and the half-saturation constant of the transporter for external fosfomycin (Ki) were determined by transport assay of [14C]glycerol-3-phosphate catalyzed by recombinant GlpT. Efficacy of fosfomycin on growth rates of GlpT defective bacteria strains transformed with recombinant GlpT was measured.Results
Fosfomycin, externally added to the proteoliposomes, poorly inhibited the glycerol-3-phosphate/glycerol-3-phosphate antiport catalyzed by the reconstituted transporter with an IC50 of 6.4 mM. A kinetic analysis revealed that the inhibition was completely competitive, that is, fosfomycin interacted with the substrate-binding site and the Ki measured was 1.65 mM. Transport assays performed with proteoliposomes containing internal fosfomycin indicate that it was not very well transported by GlpT. Complementation study, performed with GlpT defective bacteria strains, indicated that the fosfomycin resistance, beside deficiency in antibiotic transporter, could be due to other gene defects.Conclusions
The poor transport observed in a reconstituted system together with the high value of Ki and the results of complementation study well explain the usual high dosage of this drug for the treatment of the urinary tract infections.General significance
This is the first report regarding functional analysis of interaction between fosfomycin and GlpT. 相似文献83.
David Gmez‐Blanco Simone Santoro Antoni Borrs Josep Cabrera Juan Carlos Senar Pim Edelaar 《Journal of avian biology》2019,50(12)
Dozens of morphologically differentiated populations, subspecies and species of crossbills (genus Loxia) exist. It has been suggested that this divergence is due to variation in the conifer cones that each population specialises upon, requiring a specific beak size to efficiently separate the cone scales. If so, apparent survival should depend on beak size. To test this hypothesis, we undertook multievent capture–recapture modelling for 6844 individuals monitored during 27 years in a Pyrenean common crossbill L. curvirostra population in a forest of mountain pine Pinus uncinata. Apparent survival was indeed related to beak width, resulting in stabilizing selection around an optimum that was close to the observed mean beak width, indicating that local crossbill beak morphology is adapted to the conifer they feed upon. Both natural selection (selective mortality) and selective emigration of maladapted individuals may explain our findings. As is often the case in capture–recapture analyses but rarely recognised, we could not formally decompose apparent survival into selective mortality versus selective permanent emigration. Nonetheless, there are several indications that selective permanent emigration should not be fully excluded. First, natural selection by itself would have to be unusually strong compared to other empirical estimates to create the observed pattern of apparent survival. Second, the observed mean beak width was a bit lower than the estimated optimum beak width. This can be explained by immigration of crossbills with smaller beaks originating from southern populations, which may subsequently have left the study area permanently in response to low food intake. This is in line with a detected transient effect in the data, yet apparently little influx from crossbills from northern Europe. When permanent emigration is phenotypically selective this will have ecological and evolutionary consequences, so this possibility deserves more attention in general. 相似文献
84.
Crotamine, a basic neurotoxic protein, was isolated from the venom of the Southern Brazilian rattlesnake (Crotalus durissus terrificus) by gel filtration. The isolated protein showed a single band on PAGE at pH 4.5 and 7% (w/v) gel concentration, but two or more bands at 14% gel concentration, even in the presence of 4 M urea. After reduction and carboxymethylation, however, a single band was again detected. SDS-PAGE as well as ultracentrifugal analysis of the native (NC) and of the reduced and carboxymethylated (RCC) crotamine revealed a molecular weight of 4,500-5,000 for RCC and 9,000-10,000 for NC. Both components of a two-band crotamine preparation were isolated by preparative PAGE and characterized. Their particular electrophoretic mobility was retained. Their amino acid composition. N-terminal residue, and apparent toxicity were the same as those of the original sample. It was concluded that crotamine is able to form a dimer of 9,760 Da with two identical polypeptide chains crosslinked by interchain disulfide bonds and a shape not very far from spherical, which covalently binds extra subunits of 4,880 Da each. 相似文献
85.
Carey E. Gleason N. Maritza Dowling Whitney Wharton JoAnn E. Manson Virginia M. Miller Craig S. Atwood Eliot A. Brinton Marcelle I. Cedars Rogerio A. Lobo George R. Merriam Genevieve Neal-Perry Nanette F. Santoro Hugh S. Taylor Dennis M. Black Matthew J. Budoff Howard N. Hodis Frederick Naftolin S. Mitchell Harman Sanjay Asthana 《PLoS medicine》2015,12(6)
Background
Menopausal hormone therapy (MHT) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women, and whether MHT affects mood in younger women. The ancillary Cognitive and Affective Study (KEEPS-Cog) of the Kronos Early Estrogen Prevention Study (KEEPS) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women.Methods and Findings
KEEPS, a randomized, double-blinded, placebo-controlled clinical trial, was conducted at nine US academic centers. Of the 727 women enrolled in KEEPS, 693 (95.3%) participated in the ancillary KEEPS-Cog, with 220 women randomized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens (o-CEE) plus 200 mg/d micronized progesterone (m-P) for the first 12 d of each month, 211 women randomized to receive 50 μg/d transdermal estradiol (t-E2) plus 200 mg/d m-P for the first 12 d of each month, and 262 women randomized to receive placebo pills and patches. Primary outcomes included the Modified Mini-Mental State examination; four cognitive factors: verbal learning/memory, auditory attention/working memory, visual attention/executive function, and speeded language/mental flexibility; and a mood measure, the Profile of Mood States (POMS). MHT effects were analyzed using linear mixed-effects (LME) models, which make full use of all available data from each participant, including those with missing data. Data from those with and without full data were compared to assess for potential biases resulting from missing observations. For statistically significant results, we calculated effect sizes (ESs) to evaluate the magnitude of changes.On average, participants were 52.6 y old, and 1.4 y past their last menstrual period. By month 48, 169 (24.4%) and 158 (22.8%) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment (3MS and cognitive factors) and mood evaluations (POMS), respectively. However, because LME models make full use all available data, including data from women with missing data, 95.5% of participants were included in the final analysis (n = 662 in cognitive analyses, and n = 661 in mood analyses). To be included in analyses, women must have provided baseline data, and data from at least one post-baseline visit. The mean length of follow-up was 2.85 y (standard deviation [SD] = 0.49) for cognitive outcomes and 2.76 (SD = 0.57) for mood outcomes. No treatment-related benefits were found on cognitive outcomes. For mood, model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment, compared to women on placebo. The model estimate for the depression subscale was −5.36 × 10−2 (95% CI, −8.27 × 10−2 to −2.44 × 10−2; ES = 0.49, p < 0.001) and for the anxiety subscale was −3.01 × 10−2 (95% CI, −5.09 × 10−2 to −9.34 × 10−3; ES = 0.26, p < 0.001). Mood outcomes for women randomized to t-E2 were similar to those for women on placebo. Importantly, the KEEPS-Cog results cannot be extrapolated to treatment longer than 4 y.Conclusions
The KEEPS-Cog findings suggest that for recently postmenopausal women, MHT did not alter cognition as hypothesized. However, beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE, but not with 4 y of t-E2. The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles.Trial Registration
ClinicalTrials.gov NCT00154180 and NCT00623311 相似文献86.
Mishto M Ligorio C Bellavista E Martucci M Santoro A Giulioni M Marucci G Franceschi C 《Biochemical and biophysical research communications》2011,(1):65-70
Immunoproteasome has been associated to neurodegenerative and autoimmune diseases as a marker and regulator of inflammatory mechanisms. Its expression in the brain may occur upon neuroinflammation in different cell types and affect a variety of homeostatic and inflammatory pathways including the oxidized protein clearance and the self-antigen presentation. In the present study we investigated the immunoproteasome expression in hippocampi and cortex of patients affected by different histopathological forms of pharmaco-resistent mesial temporal lobe epilepsy. We identified a pathology-specific pattern of immunoproteasome expression, which could provide insight into the complex neuroinflammatory pathogenic components of this disease. 相似文献
87.
V. Tranchida‐Lombardo M. Roy E. Bugot G. Santoro Ü. Püttsepp M. Selosse S. Cozzolino 《Plant biology (Stuttgart, Germany)》2010,12(4):659-667
Several green orchids of the Neottieae tribe acquire organic carbon both from their mycorrhizal fungi and from photosynthesis. This strategy may represent an intermediate evolutionary step towards mycoheterotrophy of some non‐photosynthetic (albino) orchids. Mixed populations of green and albino individuals possibly represent a transient evolutionary stage offering opportunities to understand the evolution of mycoheterotrophy. In order to understand the emergence of albinos, we investigated patterns of spatial and genetic relationships among green and albino individuals in three mixed populations of Cephalanthera damasonium and one of C. longifolia using spatial repartition and Amplified fragment length polymorphism (AFLP) markers. Two of these populations were monitored over two consecutive flowering seasons. In spatial repartition analyses, albino individuals did not aggregate more than green individuals. Genetic analyses revealed that, in all sampled populations, albino individuals did not represent a unique lineage, and that albinos were often closer related to green individuals than to other albinos from the same population. Genetic and spatial comparison of genets from the 2‐year monitoring revealed that: (i) albinos had lower survival than green individuals; (ii) accordingly, albinos detected in the first year did not correspond to the those sampled in the second year; and (iii) with one possible exception, all examined albinos did not belong to any green genet from the same and/or from the previous year, and vice versa. Our results support a scenario of repeated insurgence of the albino phenotypes within the populations, but unsuccessful transition between the two contrasting phenotypes. Future studies should try to unravel the genetic and ecological basis of the two phenotypes. 相似文献
88.
Coinfection of SCID-hu Thy/Liv mice with human herpesvirus 6 and human immunodeficiency virus type 1 下载免费PDF全文
Gobbi A Stoddart CA Locatelli G Santoro F Bare C Linquist-Stepps V Moreno ME Abbey NW Herndier BG Malnati MS McCune JM Lusso P 《Journal of virology》2000,74(18):8726-8731
Human herpesvirus 6 (HHV-6) has been proposed as a potential cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We used the SCID-hu Thy/Liv mouse model to evaluate the in vivo interactions between HHV-6 and HIV-1. Our results demonstrate that HHV-6 and HIV-1 can simultaneously replicate in the human thymus in vivo. In this model, however, the presence of one virus appears not to modify the replication or cytopathicity of the other. 相似文献
89.
Salvatore Arpaia Luigi De Marzo Grazia M. Di Leo Maria E. Santoro Giuseppe Mennella Joop J.A. van Loon 《Entomologia Experimentalis et Applicata》2000,95(1):31-37
Colorado potato beetle (Leptinotarsa decemlineata Say) adult longevity and fecundity were studied on transgenic potato clones expressing a Cry3B endotoxin of Bacillus thuringiensis (Bt). Adult longevity and fitness were studied for the first 3 weeks after emergence. Beetle reproductive biology on highly resistant clones, intermediary resistant clones and control potato plants was monitored by dissecting females after 7–15 days of feeding and also by analysing haemolymph protein content after 3 days of feeding. Feeding behaviour on transgenic plants expressing high toxin concentrations and on control plants was monitored individually for 36 newly emerged adult beetles feeding on leaf disks during the first two meals. Lethal Time50 for adult beetles feeding on transgenic clones as the sole source of food was not significantly shorter than for beetles on control clones reared in a growth chamber. Differences tended to be larger when the experiment was conducted in a greenhouse with a less optimal temperature range (LT50 = 9.52 and 10.45 days for two transgenic clones and 13.86 for control). In contrast, female egg production on transgenic plants was almost totally inhibited. Dissection studies indicated that adult males living on high-level Bt-expressing transgenic potatoes were still able to mate and produce mobile sperm, but the females were impaired in their reproductive ability since their ovaries were generally not fully developed. An examination of the haemolymph revealed the protein concentration in females living on transgenic plants to be dramatically reduced ( 50%), and electrophoresis showed a reduced content of vitellogenin in these samples.Feeding behaviour of adult Colorado potato beetles was not affected by the different food plants; this indicates that transgenic potato plants were readily accepted as host plants by beetles. The effects of these findings on the use of transgenic plants as a means of L. decemlineata control are discussed. 相似文献
90.
Human serine racemase: moleular cloning, genomic organization and functional analysis 总被引:2,自引:0,他引:2
High levels of D-serine are found in mammalian brain, where it is an endogenous agonist of the strichinine-insensitive site of N-methyl D-aspartate type of glutamate receptors. D-serine is enriched in protoplasmic astrocytes that occur in gray matter areas of the brain and was shown to be synthesized from L-serine. We now report cloning and expression of human serine racemase, an enzyme that catalyses the synthesis of D-serine from L-serine. The enzyme displays a high homology to the murine serine racemase. It contains a pyridoxal 5'-phosphate attachment sequence similar to bacterial biosynthetic threonine dehydratase. Northern-blot analysis show high levels of human serine racemase in areas known to contain large amounts of endogenous D-serine, such as hippocampus and corpus callosum. Robust synthesis of D-serine was detected in cells transfected with human serine racemase, demonstrating the conservation of D-amino acid metabolism in humans. Serine racemase may be a therapeutic target in psychiatric diseases as supplementation of D-serine greatly improves schizophrenia symptoms. We identify the human serine racemase genomic structure and show that the gene encompasses seven exons and localizes to chromosome 17q13.3. Identification of the intron-exon boundaries of the human serine racemase gene will be useful to search for mutations in neuropsychiatric disorders. 相似文献