全文获取类型
收费全文 | 3038篇 |
免费 | 289篇 |
国内免费 | 2篇 |
出版年
2024年 | 2篇 |
2023年 | 23篇 |
2022年 | 79篇 |
2021年 | 125篇 |
2020年 | 82篇 |
2019年 | 94篇 |
2018年 | 97篇 |
2017年 | 86篇 |
2016年 | 140篇 |
2015年 | 216篇 |
2014年 | 233篇 |
2013年 | 278篇 |
2012年 | 302篇 |
2011年 | 251篇 |
2010年 | 178篇 |
2009年 | 115篇 |
2008年 | 215篇 |
2007年 | 176篇 |
2006年 | 161篇 |
2005年 | 140篇 |
2004年 | 104篇 |
2003年 | 88篇 |
2002年 | 73篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 11篇 |
1998年 | 14篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 5篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
排序方式: 共有3329条查询结果,搜索用时 15 毫秒
51.
Matthew Maddocks Vanessa Halliday Alpna Chauhan Victoria Taylor Annmarie Nelson Cathy Sampson Anthony Byrne Gareth Griffiths Andrew Wilcock 《PloS one》2013,8(12)
Background
A reduced exercise capacity is associated with increased morbidity and mortality in patients with advanced non-small cell lung cancer (NSCLC). Therapeutic exercise can be beneficial and neuromuscular electrical stimulation (NMES) of the quadriceps muscles may represent a practical approach. The primary aim of this study was to determine the acceptability of NMES of the quadriceps to patients with NSCLC used alongside palliative chemotherapy. Secondary aims explored aspects of safety and efficacy of NMES in this setting.Methods
Patients with advanced NSCLC due to receive first-line palliative chemotherapy were randomized to usual care with or without NMES. They were asked to undertake 30 minute sessions of NMES, ideally daily, but as a minimum, three times weekly. For NMES to be considered acceptable, it was predetermined that ≥80% of patients should achieve this minimum level of adherence. Qualitative interviews were held with a subset of patients to explore factors influencing adherence. Safety was assessed according to the Common Terminology Criteria for Adverse Events. Quadriceps muscle strength, thigh lean mass, and physical activity level were assessed at baseline and after three cycles of chemotherapy.Results
49 patients (28 male, median (IQR) age 69 (64−75) years) participated. Of 30 randomized to NMES, 18 were eligible for the primary endpoint, of whom 9 (50% [90% CI, 29 to 71]) met the minimum level of adherence. Adherence was enhanced by incorporating sessions into a daily routine and hindered by undesirable effects of chemotherapy. There were no serious adverse events related to NMES, nor significant differences in quadriceps muscle strength, thigh lean mass or physical activity level between groups.Conclusions
NMES is not acceptable in this setting, nor was there a suggestion of benefit. The need remains to explore NMES in patients with cancer in other settings.Trial Registration
Current Controlled Trials ISRCTN 42944026 www.controlled-trials.com/ISRCTN42944026 相似文献52.
Hianara A. Bustamante Andrés Rivera-Dictter Viviana A. Cavieres Vanessa C. Mu?oz Alexis González Yimo Lin Gonzalo A. Mardones Patricia V. Burgos 《PloS one》2013,8(12)
Alzheimer’s disease (AD) is characterized by the buildup of amyloid-β peptides (Aβ) aggregates derived from proteolytic processing of the β-amyloid precursor protein (APP). Amyloidogenic cleavage of APP by β-secretase/BACE1 generates the C-terminal fragment C99/CTFβ that can be subsequently cleaved by γ-secretase to produce Aβ. Growing evidence indicates that high levels of C99/CTFβ are determinant for AD. Although it has been postulated that γ-secretase-independent pathways must control C99/CTFβ levels, the contribution of organelles with degradative functions, such as the endoplasmic reticulum (ER) or lysosomes, is unclear. In this report, we investigated the turnover and amyloidogenic processing of C99/CTFβ in human H4 neuroglioma cells, and found that C99/CTFβ is localized at the Golgi apparatus in contrast to APP, which is mostly found in endosomes. Conditions that localized C99/CTFβ to the ER resulted in its degradation in a proteasome-dependent manner that first required polyubiquitination, consistent with an active role of the ER associated degradation (ERAD) in this process. Furthermore, when proteasomal activity was inhibited C99/CTFβ was degraded in a chloroquine (CQ)-sensitive compartment, implicating lysosomes as alternative sites for its degradation. Our results highlight a crosstalk between degradation pathways within the ER and lysosomes to avoid protein accumulation and toxicity. 相似文献
53.
Adam C. Levine Richard M. Munyaneza Justin Glavis-Bloom Vanessa Redditt Hannah C. Cockrell Bantu Kalimba Valentin Kabemba Juvenal Musavuli Mathias Gakwerere Jean Paul de Charles Umurungi Sachita P. Shah Peter C. Drobac 《PloS one》2013,8(12)
Objective
To investigate the accuracy of three clinical scales for predicting severe disease (severe dehydration or death) in children with diarrhea in a resource-limited setting.Methods
Participants included 178 children admitted to three Rwandan hospitals with diarrhea. A local physician or nurse assessed each child on arrival using the World Health Organization (WHO) severe dehydration scale and the Centers for Disease Control (CDC) scale. Children were weighed on arrival and daily until they achieved a stable weight, with a 10% increase between admission weight and stable weight considered severe dehydration. The Clinical Dehydration Scale was then constructed post-hoc using the data collected for the other two scales. Receiver Operator Characteristic (ROC) curves were constructed for each scale compared to the composite outcome of severe dehydration or death.Results
The WHO severe dehydration scale, CDC scale, and Clinical Dehydration Scale had areas under the ROC curves (AUCs) of 0.72 (95% CI 0.60, 0.85), 0.73 (95% CI 0.62, 0.84), and 0.80 (95% CI 0.71, 0.89), respectively, in the full cohort. Only the Clinical Dehydration Scale was a significant predictor of severe disease when used in infants, with an AUC of 0.77 (95% CI 0.61, 0.93), and when used by nurses, with an AUC of 0.78 (95% CI 0.63, 0.93).Conclusions
While all three scales were moderate predictors of severe disease in children with diarrhea, scale accuracy varied based on provider training and age of the child. Future research should focus on developing or validating clinical tools that can be used accurately by nurses and other less-skilled providers to assess all children with diarrhea in resource-limited settings. 相似文献54.
Alicia Ely Yamin Vanessa M. Boulanger Kathryn L. Falb Jane Shuma Jennifer Leaning 《PloS one》2013,8(8)
Background
Little is known about the interconnectedness of maternal deaths and impacts on children, beyond infants, or the mechanisms through which this interconnectedness is established. A study was conducted in rural Tanzania to provide qualitative insight regarding how maternal mortality affects index as well as other living children and to identify shared structural and social factors that foster high levels of maternal mortality and child vulnerabilities.Methods and Findings
Adult family members of women who died due to maternal causes (N = 45) and key stakeholders (N = 35) participated in in-depth interviews. Twelve focus group discussions were also conducted (N = 83) among community leaders in three rural regions of Tanzania. Findings highlight the widespread impact of a woman’s death on her children’s health, education, and economic status, and, by inference, the roles that women play within their families in rural Tanzanian communities.Conclusions
The full costs of failing to address preventable maternal mortality include intergenerational impacts on the nutritional status, health, and education of children, as well as the economic capacity of families. When setting priorities in a resource-poor, high maternal mortality country, such as Tanzania, the far-reaching effects that reducing maternal deaths can have on families and communities, as well as women’s own lives, should be considered. 相似文献55.
Erin P. Price Derek S. Sarovich Jessica R. Webb Jennifer L. Ginther Mark Mayo James M. Cook Meagan L. Seymour Mirjam Kaestli Vanessa Theobald Carina M. Hall Joseph D. Busch Jeffrey T. Foster Paul Keim David M. Wagner Apichai Tuanyok Talima Pearson Bart J. Currie 《PloS one》2013,8(8)
Burkholderia ubonensis is an environmental bacterium belonging to the Burkholderia cepacia complex (Bcc), a group of genetically related organisms that are associated with opportunistic but generally nonfatal infections in healthy individuals. In contrast, the near-neighbour species Burkholderia pseudomallei causes melioidosis, a disease that can be fatal in up to 95% of cases if left untreated. B. ubonensis is frequently misidentified as B. pseudomallei from soil samples using selective culturing on Ashdown’s medium, reflecting both the shared environmental niche and morphological similarities of these species. Additionally, B. ubonensis shows potential as an important biocontrol agent in B. pseudomallei-endemic regions as certain strains possess antagonistic properties towards B. pseudomallei. Current methods for characterising B. ubonensis are laborious, time-consuming and costly, and as such this bacterium remains poorly studied. The aim of our study was to develop a rapid and inexpensive real-time PCR-based assay specific for B. ubonensis. We demonstrate that a novel B. ubonensis-specific assay, Bu550, accurately differentiates B. ubonensis from B. pseudomallei and other species that grow on selective Ashdown’s agar. We anticipate that Bu550 will catalyse research on B. ubonensis by enabling rapid identification of this organism from Ashdown’s-positive colonies that are not B. pseudomallei. 相似文献
56.
Yann Lamarre Marie-Laure Lalanne-Mistrih Marc Romana Nathalie Lemonne Daniele Mougenel Xavier Waltz Beno?t Tressières Maryse Etienne-Julan Vanessa Tarer Marie-Dominique Hardy-Dessources Philippe Connes 《PloS one》2013,8(6)
Patients with sickle cell anemia (SCA) have usually lower diastolic, systolic and mean blood pressure (BP) than the general population. However, BP values ≥120/70 mmHg considerably increase the risk for acute and chronic complications in SCA. The aim of this study was to identify biological factors associated with relative hypertension in adults with SCA. We compared the hematological, lipid and hemolytic profiles, as well as blood viscosity, between SCA patients with normal BP (<120/70 mmHg, n = 54) and those with relative hypertension (BP≥120/70 mmHg, n = 43). Our results demonstrated that male gender (OR: 3.49; 95%CI 1.20 to 10.16, p<0.05), triglycerides (OR: 9.19; 95% CI 2.29 to 36.95, p<0.01), blood viscosity (OR: 1.35; 95% CI 1.01 to 1.81, p<0.05) and body mass index (OR: 1.37; 95% CI 1.14 to 1.64, p<0.01) were independent risks factors for relative hypertension in SCA. No association was found between the BP status and the positive history of painful vaso-occlusive crisis or acute chest syndrome. An association between triglycerides level and the occurrence of these two major acute complications was detected. Our study suggests that male gender, increased triglycerides level, BMI and blood viscosity could increase the risk for developing relative hypertension in SCA. In addition, our results support a role of moderately elevated triglycerides in the pathophysiology of vaso-occlusive events. 相似文献
57.
Diogo Jurelevicius Vanessa Marques Alvarez Raquel Peixoto Alexandre S. Rosado Lucy Seldin 《PloS one》2013,8(6)
The alkane monooxygenase AlkB, which is encoded by the alkB gene, is a key enzyme involved in bacterial alkane degradation. To study the alkB gene within bacterial communities, researchers need to be aware of the variations in alkB nucleotide sequences; a failure to consider the sequence variations results in the low representation of the diversity and richness of alkane-degrading bacteria. To minimize this shortcoming, the use of a combination of three alkB-targeting primers to enhance the detection of the alkB gene in previously isolated alkane-degrading bacteria was proposed. Using this approach, alkB-related PCR products were detected in 79% of the strains tested. Furthermore, the chosen set of primers was used to study alkB richness and diversity in different soils sampled in Carmópolis, Brazil and King George Island, Antarctica. The DNA extracted from the different soils was PCR amplified with each set of alkB-targeting primers, and clone libraries were constructed, sequenced and analyzed. A total of 255 alkB phylotypes were detected. Venn diagram analyses revealed that only low numbers of alkB phylotypes were shared among the different libraries derived from each primer pair. Therefore, the combination of three alkB-targeting primers enhanced the richness of alkB phylotypes detected in the different soils by 45% to 139%, when compared to the use of a single alkB-targeting primer. In addition, a dendrogram analysis and beta diversity comparison of the alkB composition showed that each of the sampling sites studied had a particular set of alkane-degrading bacteria. The use of a combination of alkB primers was an efficient strategy for enhancing the detection of the alkB gene in cultivable bacteria and for better characterizing the distribution of alkane-degrading bacteria in different soil environments. 相似文献
58.
59.
Xavier Waltz Marc Romana Marie-Dominique Hardy-Dessources Yann Lamarre Lydia Divialle-Doumdo Marie Petras Vanessa Tarer Régine Hierso Kizzy-Clara Baltyde Beno?t Tressières Marie-Laure Lalanne-Mistrih Fréderic Maillard Olivier Hue Maryse Etienne-Julan Philippe Connes 《PloS one》2013,8(10)
The six-minute walk test is a well-established submaximal exercise reflecting the functional status and the clinical severity of sickle cell patients. The aim of the present cross-sectional study was to investigate the biological determinants of the six-minute walk test performance in children with sickle cell anemia. Hematological and hemorheological parameters, pulmonary function and the six-minute walk test performance were determined in 42 children with sickle cell anemia at steady state. The performance during the six-minute walk test was normalized for age, sex and height and expressed as percentage of the predicted six-minute walk distance. We showed that a high level of anemia, a low fetal hemoglobin expression and low red blood cell deformability were independent predictors of a low six-minute walk test performance. This study describes for the first time the impact of blood rheology in the six-minute walk test performance in children with sickle cell anemia. 相似文献
60.
Marga G. A. Goris Vanessa Kikken Masja Straetemans Sandra Alba Marco Goeijenbier Eric C. M. van Gorp Kimberly R. Boer Jiri F. P. Wagenaar Rudy A. Hartskeerl 《PloS one》2013,8(10)