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91.
92.
Eike Gallmeier Dominik C. Bader Lydia Kriegl Sabina Berezowska Hendrik Seeliger Burkhard G?ke Thomas Kirchner Christiane Bruns Enrico N. De Toni 《PloS one》2013,8(2)
Introduction
Agonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity.Aims and Methods
Applying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated.Results
The fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p<0.001, TRAIL-R2: p = 0.006). In addition, subgroup analyses showed that loss of membrane staining for TRAIL-R2 was associated with poorer prognosis in patients without nodal metastases (multivariate Cox regression analysis, Hazard Ratio: 0.44 [95% confidence interval: 0.22−0.87]; p = 0.019). In contrast, analysis of decoy receptors TRAIL-R3 and -R4 in tumor samples showed an exclusively cytoplasmatic staining pattern and no prognostic relevance.Conclusion
This is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials. 相似文献93.
Ana M. Ortega-Prieto Julie Sheldon Ana Grande-Pérez Héctor Tejero Josep Gregori Josep Quer Juan I. Esteban Esteban Domingo Celia Perales 《PloS one》2013,8(8)
Lethal mutagenesis, or virus extinction produced by enhanced mutation rates, is under investigation as an antiviral strategy that aims at counteracting the adaptive capacity of viral quasispecies, and avoiding selection of antiviral-escape mutants. To explore lethal mutagenesis of hepatitis C virus (HCV), it is important to establish whether ribavirin, the purine nucleoside analogue used in anti-HCV therapy, acts as a mutagenic agent during virus replication in cell culture. Here we report the effect of ribavirin during serial passages of HCV in human hepatoma Huh-7.5 cells, regarding viral progeny production and complexity of mutant spectra. Ribavirin produced an increase of mutant spectrum complexity and of the transition types associated with ribavirin mutagenesis, resulting in HCV extinction. Ribavirin-mediated depletion of intracellular GTP was not the major contributory factor to mutagenesis since mycophenolic acid evoked a similar decrease in GTP without an increase in mutant spectrum complexity. The intracellular concentration of the other nucleoside-triphosphates was elevated as a result of ribavirin treatment. Mycophenolic acid extinguished HCV without an intervening mutagenic activity. Ribavirin-mediated, but not mycophenolic acid-mediated, extinction of HCV occurred via a decrease of specific infectivity, a feature typical of lethal mutagenesis. We discuss some possibilities to explain disparate results on ribavirin mutagenesis of HCV. 相似文献
94.
We define gaze agency as the awareness of the causal effect of one’s own eye movements in gaze-contingent environments, which might soon become a widespread reality with the diffusion of gaze-operated devices. Here we propose a method for measuring gaze agency based on self-monitoring propensity and sensitivity. In one task, naïf observers watched bouncing balls on a computer monitor with the goal of discovering the cause of concurrently presented beeps, which were generated in real-time by their saccades or by other events (Discovery Task). We manipulated observers’ self-awareness by pre-exposing them to a condition in which beeps depended on gaze direction or by focusing their attention to their own eyes. These manipulations increased propensity to agency discovery. In a second task, which served to monitor agency sensitivity at the sensori-motor level, observers were explicitly asked to detect gaze agency (Detection Task). Both tasks turned out to be well suited to measure both increases and decreases of gaze agency. We did not find evident oculomotor correlates of agency discovery or detection. A strength of our approach is that it probes self-monitoring propensity–difficult to evaluate with traditional tasks based on bodily agency. In addition to putting a lens on this novel cognitive function, measuring gaze agency could reveal subtle self-awareness deficits in pathological conditions and during development. 相似文献
95.
Paolo Ruggeri Andrea Splendiani Cristina Di Muri Tatiana Fioravanti Alberto Santojanni Iole Leonori Andrea De Felice Ilaria Biagiotti Piera Carpi Enrico Arneri Paola Nisi Cerioni Massimo Giovannotti Vincenzo Caputo Barucchi 《PloS one》2016,11(3)
It is well known that temporal fluctuations in small populations deeply influence evolutionary potential. Less well known is whether fluctuations can influence the evolutionary potentials of species with large census sizes. Here, we estimated genetic population parameters from as survey of polymorphic microsatellite DNA loci in archived otoliths from Adriatic European anchovy (Engraulis encrasicolus), a fish with large census sizes that supports numerous local fisheries. Stocks have fluctuated greatly over the past few decades, and the Adriatic fishery collapsed in 1987. Our results show a significant reduction of mean genetic parameters as a consequence of the population collapse. In addition, estimates of effective population size (Ne) are much smaller than those expected in a fishes with large population census sizes (Nc). Estimates of Ne indicate low effective population sizes, even before the population collapse. The ratio Ne/Ne ranged between 10−6 and 10−8, indicating a large discrepancy between the anchovy gene pool and population census size. Therefore, anchovy populations may be more vulnerable to fishery effort and environmental change than previously thought. 相似文献
96.
Phytotoxic Effects and Phytochemical Fingerprinting of Hydrodistilled Oil,Enriched Fractions,and Isolated Compounds Obtained from Cryptocarya massoy (Oken) Kosterm. Bark
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Enrico Rolli Matteo Marieschi Silvia Maietti Alessandra Guerrini Alessandro Grandini Gianni Sacchetti Renato Bruni 《化学与生物多样性》2016,13(1):66-76
The hydrodistilled oil of Cryptocarya massoy bark was characterized by GC‐FID and GC/MS analyses, allowing the identification of unusual C10 massoia lactone ( 3 , 56.2%), C12 massoia lactone ( 4 , 16.5%), benzyl benzoate ( 1 , 12.7%), C8 massoia lactone (3.4%), δ‐decalactone ( 5 , 1.5%), and benzyl salicylate ( 2 , 1.8%) as main constituents. The phytotoxic activities of the oil, three enriched fractions (lactone‐rich, ester‐rich, and sesquiterpene‐rich), and four constituents (compounds 1, 2, 5 , and δ‐dodecalactone ( 6 )) against Lycopersicon esculentum and Cucumis sativus seeds and seedlings were screened. At a concentration of 1000 μl/l, the essential oil and the massoia lactone‐rich fraction caused a complete inhibition of the germination of both seeds, and, when applied on tomato plantlets, they induced an 85 and 100% dieback, respectively. These performances exceeded those of the well‐known phytotoxic essential oils of Syzygium aromaticum and Cymbopogon citratus, already used in commercial products for the weed and pest management. The same substances were also evaluated against four phytopathogenic bacteria and ten phytopathogenic fungi, providing EC50 values against the most susceptible strains in the 100–500 μl/l range for the essential oil and in the 10–50 μl/l range for compound 6 and the lactone‐rich fraction. The phytotoxic behavior was related mainly to massoia lactones and benzyl esters, while a greater amount of 6 may infer a good activity against some phytopathogenic fungi. Further investigations of these secondary metabolites are warranted, to evaluate their use as natural herbicides. 相似文献
97.
Alfredo Vizzini Angela Lantieri Gianfranco Medardi Enrico Ercole Gabriele Cacialli 《Mycological Progress》2016,15(8):883-901
This study was focused on species of Peziza belonging to the “P. ammophila” complex, using both morphological and molecular approaches. Molecular and morphological analyses showed that several taxa are hidden under the name “ammophila” and, as a consequence, two additional species and one form are established: P. hellenica sp. nov., P. oceanica sp. nov. and P. ammophila f. megaspora f. nov. On the basis of the data that we have, these taxa seem to be related to some geographical areas; P. ammophila appears to be prevalent in northern, central and southern Europe, its f. megaspora is distributed in France and in the Netherlands, P. hellenica comes from Greece and P. oceanica from New Zealand. A cryptic species, not yet circumscribed satisfactorily, is described as P. deceptiva ad int. Moreover, the problem concerning the identification of P. ammophila is raised, the species is epitypified with a sequenced collection from Sicily (Italy) and a key to the species of the complex is provided. 相似文献
98.
Vincenzo De Cicco Massimo Barresi Maria Paola Tramonti Fantozzi Enrico Cataldo Vincenzo Parisi Diego Manzoni 《PloS one》2016,11(2)
Several studies have demonstrated that chewing can be regarded as a preventive measure for cognitive impairment, whereas masticatory deficiency, associated with soft-diet feeding, is a risk factor for the development of dementia. At present the link between orofacial sensorimotor activity and cognitive functions is unknown. In subjects with unilateral molar loss we have shown asymmetries in both pupil size and masticatory muscles electromyographic (EMG) activity during clenching: the molar less side was characterized by a lower EMG activity and a smaller pupil. Since implant-prostheses, greatly reduced both the asymmetry in EMG activity and in pupil’s size, trigeminal unbalance, leading to unbalance in the activity of the Locus Coeruleus (LC), may be responsible for the pupil’s asymmetry. According to the findings obtained in animal models, we propose that the different activity of the right and left LC may induce an asymmetry in brain activity, thus leading to cognitive impairment. According to this hypothesis, prostheses improved the performance in a complex sensorimotor task and increased the mydriasis associated with haptic tasks. In conclusion, the present study indicates that the implant-prosthesis therapy, which reduces the unbalance of trigeminal proprioceptive afferents and the asymmetry in pupil’s size, may improve arousal, boosting performance in a complex sensorimotor task. 相似文献
99.
Maurizio G. Paoletti Robert J. Blakemore Csaba Csuzdi Luca Dorigo Angelo Leandro Dreon Federico Gavinelli Francesca Lazzarini Nicola Manno Enzo Moretto David Porco Enrico Ruzzier Vladimiro Toniello Andrea Squartini Giuseppe Concheri Marina Zanardo Javier Alba-Tercedor 《PloS one》2016,11(3)
A new Italian earthworm morphologically close to the similarly large and anecic Eophila tellinii (Rosa, 1888) is described. Distribution of Eophila crodabepis sp. nov. extends over 750 km2 from East to West on the Asiago Plateau and Vittorio Veneto Hills, from North to South on mounts Belluno Prealps (Praderadego and Cesen), Asiago, Grappa and onto the Montello foothills. This range abuts that of Eophila tellinii in northern Friuli Venezia Giulia region. Known localities of both E. tellinii and E.crodabepis sp. nov. are mapped. mtDNA barcoding definitively separates the new western species from classical Eophila tellinii (Rosa, 1888). 相似文献
100.
Fran?ois Hug Paul W. Hodges Timothy J. Carroll Enrico De Martino Justine Magnard Kylie Tucker 《PloS one》2016,11(4)
During a force-matched bilateral task, when pain is induced in one limb, a shift of load to the non-painful leg is classically observed. This study aimed to test the hypothesis that this adaptation to pain depends on the mechanical efficiency of the non-painful leg. We studied a bilateral plantarflexion task that allowed flexibility in the relative force produced with each leg, but constrained the sum of forces from both legs to match a target. We manipulated the mechanical efficiency of the non-painful leg by imposing scaling factors: 1, 0.75, or 0.25 to decrease mechanical efficiency (Decreased efficiency experiment: 18 participants); and 1, 1.33 or 4 to increase mechanical efficiency (Increased efficiency experiment: 17 participants). Participants performed multiple sets of three submaximal bilateral isometric plantarflexions with each scaling factor during two conditions (Baseline and Pain). Pain was induced by injection of hypertonic saline into the soleus. Force was equally distributed between legs during the Baseline contractions (laterality index was close to 1; Decreased efficiency experiment: 1.16±0.33; Increased efficiency experiment: 1.11±0.32), with no significant effect of Scaling factor. The laterality index was affected by Pain such that the painful leg contributed less than the non-painful leg to the total force (Decreased efficiency experiment: 0.90±0.41, P<0.001; Increased efficiency experiment: 0.75±0.32, P<0.001), regardless of the efficiency (scaling factor) of the non-painful leg. When compared to the force produced during Baseline of the corresponding scaling condition, a decrease in force produced by the painful leg was observed for all conditions, except for scaling 0.25. This decrease in force was correlated with a decrease in drive to the soleus muscle. These data highlight that regardless of the overall mechanical cost, the nervous system appears to prefer to alter force sharing between limbs such that force produced by the painful leg is reduced relative to the non-painful leg. 相似文献