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911.
Daniel Courteix Jo?o Valente-dos-Santos Béatrice Ferry Gérard Lac Bruno Lesourd Robert Chapier Geraldine Naughton Geoffroy Marceau Manuel Jo?o Coelho-e-Silva Agnès Vinet Guillaume Walther Philippe Obert Frédéric Dutheil 《PloS one》2015,10(9)
Background
Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome (MetS). However, restrictive diets might induce bone loss. The nature of exercise and whether exercise with weight loss programs can protect against potential bone mass deficits remains unclear. Moreover, compliance is essential in intervention programs. Thus, we aimed to investigate the effects that modality and exercise compliance have on bone mineral content (BMC) and density (BMD).Methods
We investigated 90 individuals with MetS who were recruited for the 1-year RESOLVE trial. Community-dwelling seniors with MetS were randomly assigned into three different modalities of exercise (intensive resistance, intensive endurance, moderate mixed) combined with a restrictive diet. They were compared to 44 healthy controls who did not undergo the intervention.Results
This intensive lifestyle intervention (15–20 hours of training/week + restrictive diet) resulted in weight loss, body composition changes and health improvements. Baseline BMC and BMD for total body, lumbar spine and femoral neck did not differ between MetS groups and between MetS and controls. Despite changes over time, BMC or BMD did not differ between the three modalities of exercise and when compared with the controls. However, independent of exercise modality, compliant participants increased their BMC and BMD compared with their less compliant peers. Decreases in total body lean mass and negative energy balance significantly and independently contributed to decreases in lumbar spine BMC.Conclusion
After the one year intervention, differences relating to exercise modalities were not evident. However, compliance with an intensive exercise program resulted in a significantly higher bone mass during energy restriction than non-compliance. Exercise is therefore beneficial to bone in the context of a weight loss program.Trial Registration
ClinicalTrials.gov NCT00917917 相似文献912.
Nassima Benzoubir Charlotte Mussini Charlène Lejamtel Alexandre Dos Santos Claire Guillaume Christophe Desterke Didier Samuel Christian Bréchot Marie-Fran?oise Bourgeade Catherine Guettier 《PloS one》2015,10(6)
Background and Aims
The prognosis of hepatocellular carcinoma (HCC) is hampered by frequent tumour recurrence and metastases. Epithelial-Mesenchymal Transition (EMT) is now recognized as a key process in tumour invasion, metastasis and the generation of cancer initiating cells. The morphological identification of EMT in tumour samples from the expression of novel mesenchymal markers could provide relevant prognostic information and aid in understanding the metastatic process.Methods
The expression of Smooth Muscle Actins was studied using immunofluorescence and immunohistochemistry assays in cultured liver cells during an induced EMT process and in liver specimens from adult and paediatric HCC series.Results
We report here that in HCC cell lines treated with TGF-β and in HCC specimens, the expression of αSMA, a known mesenchymal marker of EMT, could never be detected. In addition, our in vitro studies identified the enteric form of SMA, γSMA, as being a marker of EMT. Moreover, this SMA isoform was expressed in 46% of 58 tumours from 42 adult HCC patients and in 90% of 16 tumours from 12 paediatric HCC patients. Interestingly, this expression was significantly correlated with poor tumour differentiation and progenitor cell features characterized by the expression of EpCAM and K19.Conclusion
Taken together, our results support the conclusion that γSMA expression in HCC is strongly correlated with the EMT process, HCC aggressiveness and the identification of cancer stem cells. This correlation suggests that γSMA represents a novel and powerful marker to predict HCC progression. 相似文献913.
Philippe Devillier Eric Garrigue Guillaume D’Auzers Nicolas Monjotin Thomas Similowski Thierry Clerc 《Respiratory research》2015,16(1)
Background
Long acting bronchodilators are the standard of care in the management of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the efficacy and safety of V0162, a novel anticholinergic agent with bronchodilator properties, in preclinical models and in patients with COPD.Methods
Guinea pigs were used to evaluate the impact of V0162 on the acetylcholine or histamine-induced bronchoconstriction. V0162 was also investigated in an allergic asthma model on ovalbumin-sensitized guinea pig. For clinical investigations, healthy volunteers were included in a dose-escalation, randomized, placebo-controlled phase I study to determine the maximal tolerated dose, followed by a randomized, placebo-controlled, cross-over phase II study in patients with COPD. V0162 was given via inhalation route. The objectives of the phase I/II study were to assess the safety and efficacy of V0162, in terms of bronchodilation and reduction in hyperinflation.Results
Preclinical results showed that V0162 was able to prevent bronchoconstriction induced either by acetylcholine or histamine. V0162 reversed the bronchoconstriction and airway inflammation caused by ovalbumin challenge in sensitized guinea pigs. In the healthy volunteers study, 88 subjects were enrolled: 66 received V0162 and 22 received placebo. No particular safety concerns were raised. The maximal tolerated dose was not reached and the dose escalation was stopped at 2400 μg. A total of 20 patients with COPD were then enrolled. All patients received a single-dose of V0162 1600 μg and of placebo in two alternating periods. In COPD patients, V0162 demonstrated a significant increase in FEV1 compared with placebo (148 ± 137 ml vs. 36 ± 151 ml, p = 0.003). This bronchodilatory effect was corroborated by a reduction in hyperinflation. There was a trend toward dyspnea relief (change in visual analog scale at 22 h, −15.1 ± 26.0 mm vs.- 5.3 ± 28.8 mm with placebo, p = 0.054). No serious adverse events (AEs) were reported. Most common AEs were productive and non-productive cough, dyspnea and pruritus.Conclusions
V0162 improved pulmonary function and tended to improve dyspnea in patients with COPD over more than 24 h. The slight plasmatic exposure observed might support the good safety profile.Trial registration
ClinicalTrials.gov identifier: NCT01348555相似文献914.
The contribution of patch‐scale conditions is greater than that of macroclimate in explaining local plant diversity in fragmented forests across Europe
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Alicia Valdés Jonathan Lenoir Emilie Gallet‐Moron Emilie Andrieu Jörg Brunet Olivier Chabrerie Déborah Closset‐Kopp Sara A. O. Cousins Marc Deconchat Pieter De Frenne Pallieter De Smedt Martin Diekmann Karin Hansen Martin Hermy Annette Kolb Jaan Liira Jessica Lindgren Tobias Naaf Taavi Paal Irina Prokofieva Michael Scherer‐Lorenzen Monika Wulf Kris Verheyen Guillaume Decocq 《Global Ecology and Biogeography》2015,24(9):1094-1105
915.
Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis
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Chris D Madsen Jesper T Pedersen Freja A Venning Lukram Babloo Singh Emad Moeendarbary Guillaume Charras Thomas R Cox Erik Sahai Janine T Erler 《EMBO reports》2015,16(10):1394-1408
Cancer‐associated fibroblasts (CAFs) interact with tumour cells and promote growth and metastasis. Here, we show that CAF activation is reversible: chronic hypoxia deactivates CAFs, resulting in the loss of contractile force, reduced remodelling of the surrounding extracellular matrix and, ultimately, impaired CAF‐mediated cancer cell invasion. Hypoxia inhibits prolyl hydroxylase domain protein 2 (PHD2), leading to hypoxia‐inducible factor (HIF)‐1α stabilisation, reduced expression of αSMA and periostin, and reduced myosin II activity. Loss of PHD2 in CAFs phenocopies the effects of hypoxia, which can be prevented by simultaneous depletion of HIF‐1α. Treatment with the PHD inhibitor DMOG in an orthotopic breast cancer model significantly decreases spontaneous metastases to the lungs and liver, associated with decreased tumour stiffness and fibroblast activation. PHD2 depletion in CAFs co‐injected with tumour cells similarly prevents CAF‐induced metastasis to lungs and liver. Our data argue that reversion of CAFs towards a less active state is possible and could have important clinical implications. 相似文献
916.
917.
Unveiling trade‐offs in resource selection of migratory caribou using a mechanistic movement model of availability
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![点击此处可从《Ecography》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Guillaume Bastille‐Rousseau Jonathan R. Potts James A. Schaefer Mark A. Lewis E. Hance Ellington Nathaniel D. Rayl Shane P. Mahoney Dennis L. Murray 《Ecography》2015,38(10):1049-1059
Habitat selection is a multi‐level, hierarchical process that should be a key component in the balance between food acquisition and predation risk avoidance (food–predation trade‐off). However, to date, studies have not fully elucidated how fine‐ and broad‐scale habitat decisions by individual prey can help balance food versus risk. We studied broad‐scale habitat selection by Newfoundland caribou Rangifer tarandus, focusing on trade‐offs between predation risk versus access to forage during the calving and post‐calving period. We improved traditional measures of habitat availability by incorporating fine‐scale movement patterns of caribou into the availability kernel, thus enabling separation of broad and fine scales of selection. Remote sensing and field surveys served to create a spatio‐temporal model of forage availability, whereas GPS telemetry locations from 66 black bears Ursus americanus and 59 coyotes Canis latrans provided models of predation risk. We then used GPS telemetry locations from 114 female caribou to assess food–predation trade‐offs through the prism of our refined model of caribou habitat availability. We noted that migratory movements of caribou were oriented mainly towards habitats with abundant forage and lower risk of bear and (to a lesser extent) coyote encounter. These findings were generally consistent across caribou herds and would not have been evident had we used traditional methods instead of our refined model when estimating habitat availability. We interpret these findings in the context of stereotypical migratory behaviour observed in Newfoundland caribou, which occurs despite the extirpation of wolves Canis lupus nearly a century ago. We submit that caribou are able to balance food acquisition against predation risk using a complex set of factors involving both finer and broader scale selection. Accordingly, our study provides a strong argument for using refined habitat availability estimates when assessing food–predation trade‐offs. 相似文献
918.
Mass spectrometry based analysis of human plasma‐derived factor X revealed novel post‐translational modifications
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Guillaume Chevreux Nolwenn Tilly Valegh Faid Nicolas Bihoreau 《Protein science : a publication of the Protein Society》2015,24(10):1640-1648
Human coagulation factor X is a central component of the blood coagulation cascade that converts, under its activated form, prothrombin into thrombin. Generation of thrombin is the final step of the clotting cascade that leads to the clot by polymerization of fibrinogen molecules into a fibrin network. Today, research of new by‐passing agents of the coagulation may contribute to an increased interest for human factor X, which may, in consequence, lead to the need of a more exhaustive picture of its structural features. Several post‐translational modifications of human factor X such as γ‐carboxylation/β‐hydroxylation of the N‐terminal light chain and N‐/O‐glycosylation of the activation peptide have been described. But, so far as we know, no comprehensive studies of its post‐translational modifications have been reported. In this article we report an exhaustive structural analysis of human factor X by mass spectrometry using successive protein and peptide mapping. Surprisingly, human factor X was found to be mostly O‐glucosylated on its light chain at Ser106 position, Ser9 of its activation peptide is phosphorylated at about 30% and its C‐terminal heavy chain is fully O‐glycosylated at Thr249 by a mucin‐type O‐glycan (HexNAc‐Hex‐NeuAc). The knowledge of these post‐translational modifications is mandatory for the development of recombinant molecules. 相似文献
919.
920.