首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2130篇
  免费   181篇
  2022年   24篇
  2021年   33篇
  2020年   26篇
  2019年   26篇
  2018年   36篇
  2017年   28篇
  2016年   49篇
  2015年   111篇
  2014年   107篇
  2013年   135篇
  2012年   196篇
  2011年   161篇
  2010年   135篇
  2009年   126篇
  2008年   139篇
  2007年   157篇
  2006年   166篇
  2005年   125篇
  2004年   138篇
  2003年   116篇
  2002年   116篇
  2001年   14篇
  2000年   20篇
  1999年   16篇
  1998年   21篇
  1997年   14篇
  1996年   12篇
  1995年   6篇
  1994年   9篇
  1993年   6篇
  1992年   6篇
  1991年   2篇
  1990年   6篇
  1989年   3篇
  1988年   2篇
  1987年   2篇
  1986年   1篇
  1985年   4篇
  1984年   3篇
  1983年   4篇
  1982年   1篇
  1980年   1篇
  1979年   2篇
  1977年   1篇
  1976年   1篇
  1974年   2篇
  1973年   1篇
  1972年   1篇
排序方式: 共有2311条查询结果,搜索用时 234 毫秒
151.

Background

Mindfulness is defined as non-judgmental awareness of the present moment. There is some evidence of the efficacy of mindfulness-based interventions in weight loss. However, this psychological concept has only been rarely explored in observational studies, and no study to date has examined the association between dispositional mindfulness and weight status in a large population-based sample.

Objective

We aimed to examine the relationship between mindfulness scores and weight status in a large sample of the adult general population in France.

Design and Methods

A total of 14,400 men and 49,228 women aged ≥18 y participating in the NutriNet-Santé study were included in this cross-sectional analysis. We collected mindfulness data using the Five Facet Mindfulness Questionnaire as well as self-reported weight and height. The association between weight status and dispositional mindfulness, as well as its subscales (observing, describing, acting with awareness, non-judging and non-reactivity), was assessed using multinomial logistic regression models adjusted for socio-demographic and lifestyle factors.

Results

Women with higher dispositional mindfulness scores were less likely to be overweight (excluding obesity) (OR quartile 4 vs. 1 = 0.84, 95% CI: 0.79-0.90) and obese (OR quartile 4 vs. 1 = 0.71, 95% CI: 0.65-0.78). In addition, overall, in this group, all subscales were inversely associated with weight status, with the strongest association found for the “observing” subscale. In men, higher mindfulness was associated only with lower odds of obesity (OR quartile 4 vs. 1 = 0.81 (0.69, 0.96)), and only the “observing” and “non-reactivity” subscales were significantly inversely associated with weight status.

Conclusion

Results support the interest of a shift in perspective that takes into account positive psychological and cognitive factors such as dispositional mindfulness in the investigation of obesity and its associated factors.  相似文献   
152.
Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD) 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2 -/-) and wild-type (Wt) alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2 -/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39), an isogenic capsule locus deletion mutant (D39Δcps) or serotype 3 S. pneumoniae (6303) via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2 -/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2 -/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2 -/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2 -/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.  相似文献   
153.
Yams (Dioscorea spp.) consist of approximately 600 species. Presently, these species are threatened by genetic erosion due to many factors such as pest attacks and farming practices. In parallel, complex taxonomic boundaries in this genus makes it more challenging to properly address the genetic diversity of yam and manage its germplasm. As a first step toward evaluating and preserving the genetic diversity yam species, we use a phylogenetic diversity (PD) approach that has the advantage to investigate phylogenetic relationships and test hypotheses of species monophyly while alleviating to the problem of ploidy variation within and among species. The Bayesian phylogenetic analysis of 62 accessions from 7 species from three regions of Cameroon showed that most Dioscorea sections were monophyletic, but species within sections were generally non-monophyletic. The wild species D. praehensilis and cultivated D. cayenensis were the species with the highest PD. At the opposite, D. esculenta has a low PD and future studies should focus on this species to properly address its conservation status. We also show that wild species show a stronger genetic structure than cultivated species, which potentially reflects the management of the yam germplasm by farmers. These findings show that phylogenetic diversity is a promising approach for an initial investigation of genetic diversity in a crop consisting of closely related species.  相似文献   
154.

Objective

The identification of a predisposition toward malignant hyperthermia (MH) as a risk factor for exertional heat stroke (EHS) remains a matter of debate. Such a predisposition indicates a causal role for MH susceptibility (MHS) after EHS in certain national recommendations and has led to the use of an in vitro contracture test (IVCT) to identify the MHS trait in selected or unselected EHS patients. The aim of this study was to determine whether the MHS trait is associated with EHS.

Methods

EHS subjects in the French Armed Forces were routinely examined for MHS after experiencing an EHS episode. This retrospective study compared the features of IVCT-diagnosed MHS (iMHS) EHS subjects with those of MH-normal EHS patients and MH patients during the 2004–2010 period. MHS status was assessed using the European protocol.

Results

During the study period, 466 subjects (median age 25 years; 31 women) underwent MHS status investigation following an EHS episode. None of the subjects reported previous MH events. An IVCT was performed in 454 cases and was diagnostic of MHS in 45.6% of the study population, of MH susceptibility to halothane in 18.5%, of MH susceptibility to caffeine in 9.9%, and of MH susceptibility to halothane and caffeine in 17.2%. There were no differences in the clinical features, biological features or outcomes of iMHS EHS subjects compared with those of MH-normal or caffeine or halothane MHS subjects without known prior EHS episode. The recurrence rate was 12.7% and was not associated with MH status or any clinical or biological features. iMHS EHS patients exhibited a significantly less informative IVCT response than MH patients.

Conclusions

The unexpected high prevalence of the MHS trait after EHS suggested a latent disturbance of calcium homeostasis that accounted for the positive IVCT results. This study did not determine whether EHS patients have an increased risk of MH, and it could not determine whether MH susceptibility is a risk factor for EHS.  相似文献   
155.

Background

Aspergillus colonisation is frequently reported after lung transplantation. The question of whether aspergillus colonisation is related to the hospital environment is crucial to prevention.

Method

To elucidate this question, a prospective study of aspergillus colonisation after lung transplantation, along with a mycological survey of the patient environment, was performed.

Results

Forty-four consecutive patients were included from the day of lung transplantation and then examined weekly for aspergillus colonisation until hospital discharge. Environmental fungal contamination of each patient was followed weekly via air and surface sampling. Twelve patients (27%) had transient aspergillus colonisation, occurring 1–13 weeks after lung transplantation, without associated manifestation of aspergillosis. Responsible Aspergillus species were A. fumigatus (6), A. niger (3), A. sydowii (1), A. calidoustus (1) and Aspergillus sp. (1). In the environment, contamination by Penicillium and Aspergillus was predominant. Multivariate analysis showed a significant association between occurrence of aspergillus colonisation and fungal contamination of the patient’s room, either by Aspergillus spp. in the air or by A.fumigatus on the floor. Related clinical and environmental isolates were genotyped in 9 cases of aspergillus colonisation. For A. fumigatus (4 cases), two identical microsatellite profiles were found between clinical and environmental isolates collected on distant dates or locations. For other Aspergillus species, isolates were different in 2 cases; in 3 cases of aspergillus colonisation by A. sydowii, A. niger and A. calidoustus, similarity between clinical and environmental internal transcribed spacer and tubulin sequences was >99%.

Conclusion

Taken together, these results support the hypothesis of environmental risk of hospital acquisition of aspergillus colonisation in lung transplant recipients.  相似文献   
156.

Background

Impact of the pathophysiology of Plasmodium falciparum placental malaria (PM) on the profile of some oxidative stress biomarkers and their relationship with poor pregnancy outcomes in women remain unknown.

Methods

Between 2013 and 2014, peripheral blood and placenta tissue from 120 Cameroonian women at delivery were assessed for maternal haemoglobin and, parasitaemia respectively. Parasite accumulation in the placenta was investigated histologically. The levels of oxidative stress biomarkers Malondialdehyde (MDA), Nitric Oxide (NO), Superoxide dismutase (SOD), Catalase (CAT) and Gluthatione (GSH) in the supernatant of teased placenta tissues were determined by Colorimetric enzymatic assays.

Results

Parasitaemia was inversely related to haemoglobin levels and birth weight (P <0.001 and 0.012, respectively). The level of lipid peroxide product (MDA) was significantly higher in the malaria infected (P = 0.0047) and anaemic (P = 0.024) women compared to their non-infected and non-anaemic counterparts, respectively. A similar trend was observed with SOD levels, though not significant. The levels of MDA also correlated positively with parasitaemia (P = 0.0024) but negatively with haemoglobin levels (P = 0.002). There was no association between parasitaemia, haemoglobin level and the other oxidative stress biomarkers. From histological studies, levels of MDA associated positively and significantly with placenta malaria infection and the presence of malaria pigments. The levels of SOD, NO and CAT increased with decreasing leukocyte accumulation in the intervillous space. Baby birth weight increased significantly with SOD and CAT levels, but decreased with levels of GSH.

Conclusions

Placental P. falciparum infection may cause oxidative stress of the placenta tissue with MDA as a potential biomarker of PM, which alongside GSH could lead to poor pregnancy outcomes (anaemia and low birth weight). This finding contributes to the understanding of the pathophysiology of P. falciparum placental malaria in women.  相似文献   
157.
Moyamoya is a cerebrovascular condition characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and the compensatory development of abnormal “moyamoya” vessels. The pathophysiological mechanisms of this condition, which leads to ischemic and hemorrhagic stroke, remain unknown. It can occur as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes). Here, we describe an autosomal-recessive disease leading to severe moyamoya and early-onset achalasia in three unrelated families. This syndrome is associated in all three families with homozygous mutations in GUCY1A3, which encodes the α1 subunit of soluble guanylate cyclase (sGC), the major receptor for nitric oxide (NO). Platelet analysis showed a complete loss of the soluble α1β1 guanylate cyclase and showed an unexpected stimulatory role of sGC within platelets. The NO-sGC-cGMP pathway is a major pathway controlling vascular smooth-muscle relaxation, vascular tone, and vascular remodeling. Our data suggest that alterations of this pathway might lead to an abnormal vascular-remodeling process in sensitive vascular areas such as ICA bifurcations. These data provide treatment options for affected individuals and strongly suggest that investigation of GUCY1A3 and other members of the NO-sGC-cGMP pathway is warranted in both isolated early-onset achalasia and nonsyndromic moyamoya.  相似文献   
158.
Buran-Kaya III site, in Crimea, provides an exceptional stratigraphic sequence, extending from Middle Paleolithic to Neolithic. Among the archaeological layers allocated to the Gravettian (sensu lato), more than 170 anthropological remains have been discovered in the layer 6-1. They represent the oldest Upper Paleolithic modern humans from Eastern Europe in a well-documented archaeological context. The aim of this article, based on dental remains and enamel dental hypoplasias in particular, is to evaluate the health of the modern humans, which lived more than 32,000 years BP ago in Crimea. This study puts into the light the low frequency of hypoplasias (occurring in the two youngest individuals). This article complete the rare studies concerning the presence of this physiological stress during the Early Upper Paleolithic and confirm the scarcity of enamel dental hypoplasias and dental pathologies, such as caries, at this period.  相似文献   
159.
The centrosome position is tightly regulated during the cell cycle and during differentiated cellular functions. Because centrosome organizes the microtubule network to coordinate both intracellular organization and cell signaling, centrosome positioning is crucial to determine either the axis of cell division, the direction of cell migration or the polarized immune response of lymphocytes. Since alteration of centrosome positioning seems to promote cell transformation and tumor spreading, the molecular mechanisms controlling centrosome movement in response to extracellular and intracellular cues are under intense investigation. Evolutionary conserved pathways involving polarity proteins and cytoskeletal rearrangements are emerging as common regulators of centrosome positioning in a wide variety of cellular contexts.  相似文献   
160.
We present a full-field technique that allows label-free cytoskeletal network imaging inside living cells. This noninvasive technique allows monitoring of the cytoskeleton dynamics as well as interactions between the latter and organelles on any timescale. It is based on high-resolution quantitative phase imaging (modified Quadriwave lateral shearing interferometry) and can be directly implemented using any optical microscope without modification. We demonstrate the capability of our setup on fixed and living Chinese hamster ovary cells, showing the cytoskeleton dynamics in lamellipodia during protrusion and mitochondria displacement along the cytoskeletal network. In addition, using the quantitative function of the technique, along with simulation tools, we determined the refractive index of a single tubulin microtubule to be ntubu = 2.36 ± 0.6 at λ = 527 nm.The cytoskeleton is mainly composed of an actin and tubulin microtubule network, and it has many important roles at the cellular scale (1). It allows the cell to modify its shape, is implied in cell migration and adhesion processes, and is used as a support for organelle displacement inside cells.Optical microscopy is useful for dynamic studies in which the cytoskeletal network is reorganizing quickly. However, due to the poor native interaction between light and this network fluorescence labeling is commonly used to image the cytoskeleton (2). Anisotropic approaches are also used on this kind of structure, as the cytoskeletal filaments may present refractive index anisotropy. Based on this property, polarized microscopy has been used to reveal the cytoskeleton (3). However, this technique is relatively slow compared to the cytoskeleton dynamics and requires perfectly stressless optics and a nondepolarizing sample. Differential interference contrast (DIC) approaches enhance the contrast in unstained cytoskeletal fibers (4) but also require precise light polarization control of both samples and optical components (for example, no plastic elements can be used for standard DIC). Moreover, the image has a gradient shape that induces loss of resolution and makes the images hard to interpret, especially in complex biological environments. Some DIC-based developments have been proposed that would make it possible to retrieve quantitative information from the sample and/or minimize the effects of depolarizing elements (5–8). Nonlinear interactions in second-harmonic generation (SHG) (9) that are sensitive to orientation and anisotropic refractive index are also applied to cytoskeleton imaging. Label-free imaging is thus obtained, but it requires a powerful laser and a scanning approach that may be too slow when fast dynamics need to be studied.Although light interaction with a nonlabeled cytoskeleton is weak, with barely any absorption, there is a signature on the beam that travels through the structure even with nonpolarized illumination/detection. Indeed, as tubulin microtubules and actin filaments are denser than the cytoplasm, their respective refractive indices are also higher (10). This means that the light is slightly delayed by the cytoskeleton, leading to a possible contrast when looking at the phase component of light. In this article, we consider quantitative phase microscopy (QPM) based on quadriwave lateral shearing interferometry (QWLSI) (11). QWLSI makes it possible to image nonlabeled cells with a conventional transillumination microscope equipped with a halogen lamp. We propose a modified version of the QWLSI presented in our previous publication (11) that allows the fast, sensitive, and highly resolved imaging required to reveal cytoskeletal network dynamics in living cells. After discussing the signal/noise ratio (SNR) of our approach, we compare QPM with immunostaining of actin and tubulin microtubules on Chinese hamster ovary (CHO) cells, demonstrating the capability of QPM to visualize the cytoskeleton. Living wild-type (wt) CHO cells are then imaged at a high frame rate (2.5 Hz) to illustrate the spatiotemporal resolution of the technique for cytoskeleton imaging.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号