全文获取类型
收费全文 | 5068篇 |
免费 | 450篇 |
出版年
2023年 | 45篇 |
2022年 | 72篇 |
2021年 | 161篇 |
2020年 | 124篇 |
2019年 | 142篇 |
2018年 | 163篇 |
2017年 | 139篇 |
2016年 | 248篇 |
2015年 | 302篇 |
2014年 | 330篇 |
2013年 | 382篇 |
2012年 | 454篇 |
2011年 | 425篇 |
2010年 | 282篇 |
2009年 | 249篇 |
2008年 | 299篇 |
2007年 | 272篇 |
2006年 | 256篇 |
2005年 | 236篇 |
2004年 | 188篇 |
2003年 | 179篇 |
2002年 | 166篇 |
2001年 | 45篇 |
2000年 | 43篇 |
1999年 | 36篇 |
1998年 | 39篇 |
1997年 | 25篇 |
1996年 | 27篇 |
1995年 | 19篇 |
1994年 | 21篇 |
1993年 | 16篇 |
1992年 | 8篇 |
1991年 | 20篇 |
1990年 | 7篇 |
1989年 | 11篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1976年 | 7篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1968年 | 2篇 |
排序方式: 共有5518条查询结果,搜索用时 31 毫秒
81.
82.
Rodolfo Carvalho Pacagnella Jo?o Paulo Souza Jill Durocher Pablo Perel Jennifer Blum Beverly Winikoff Ahmet Metin Gülmezoglu 《PloS one》2013,8(3)
Introduction
This systematic review examines the relationship between blood loss and clinical signs and explores its use to trigger clinical interventions in the management of obstetric haemorrhage.Methods
A systematic review of the literature was carried out using a comprehensive search strategy to identify studies presenting data on the relationship of clinical signs & symptoms and blood loss. Methodological quality was assessed using the STROBE checklist and the general guidelines of MOOSE.Results
30 studies were included and five were performed in women with pregnancy-related haemorrhage (other studies were carried in non-obstetric populations). Heart rate (HR), systolic blood pressure (SBP) and shock index were the parameters most frequently studied. An association between blood loss and HR changes was observed in 22 out of 24 studies, and between blood loss and SBP was observed in 17 out of 23 studies. An association was found in all papers reporting on the relationship of shock index and blood loss. Seven studies have used Receiver Operating Characteristic Curves to determine the accuracy of clinical signs in predicting blood loss. In those studies the AUC ranged from 0.56 to 0.74 for HR, from 0.56 to 0.79 for SBP and from 0.77 to 0.84 for shock index. In some studies, HR, SBP and shock index were associated with increased mortality.Conclusion
We found a substantial variability in the relationship between blood loss and clinical signs, making it difficult to establish specific cut-off points for clinical signs that could be used as triggers for clinical interventions. However, the shock index can be an accurate indicator of compensatory changes in the cardiovascular system due to blood loss. Considering that most of the evidence included in this systematic review is derived from studies in non-obstetric populations, further research on the use of the shock index in obstetric populations is needed. 相似文献83.
J. Jaime Miranda Victor M. Herrera Julio A. Chirinos Luis F. Gómez Pablo Perel Rafael Pichardo Angel González José R. Sánchez Catterina Ferreccio Ximena Aguilera Eglé Silva Myriam Oróstegui Josefina Medina-Lezama Cynthia M. Pérez Erick Suárez Ana P. Ortiz Luis Rosero Noberto Schapochnik Zulma Ortiz Daniel Ferrante Juan P. Casas Leonelo E. Bautista 《PloS one》2013,8(1)
Background
Limited knowledge on the prevalence and distribution of risk factors impairs the planning and implementation of cardiovascular prevention programs in the Latin American and Caribbean (LAC) region.Methods and Findings
Prevalence of hypertension, diabetes mellitus, abnormal lipoprotein levels, obesity, and smoking were estimated from individual-level patient data pooled from population-based surveys (1998–2007, n = 31,009) from eight LAC countries and from a national survey of the United States (US) population (1999–2004) Age and gender specific prevalence were estimated and age-gender adjusted comparisons between both populations were conducted. Prevalence of diabetes mellitus, hypertension, and low high-density lipoprotein (HDL)-cholesterol in LAC were 5% (95% confidence interval [95% CI]: 3.4, 7.9), 20.2% (95% CI: 12.5, 31), and 53.3% (95% CI: 47, 63.4), respectively. Compared to LAC region’s average, the prevalence of each risk factor tended to be lower in Peru and higher in Chile. LAC women had higher prevalence of obesity and low HDL-cholesterol than men. Obesity, hypercholesterolemia, and hypertriglyceridemia were more prevalent in the US population than in LAC population (31 vs. 16.1%, 16.8 vs. 8.9%, and 36.2 vs. 26.5%, respectively). However, the prevalence of low HDL-cholesterol was higher in LAC than in the US (53.3 vs. 33.7%).Conclusions
Major cardiovascular risk factors are highly prevalent in LAC region, in particular low HDL-cholesterol. In addition, marked differences do exist in this prevalence profile between LAC and the US. The observed patterns of obesity-related risk factors and their current and future impact on the burden of cardiovascular diseases remain to be explained. 相似文献84.
Andrea Gottlieb Hans-Georg Müller Alicia N. Massa Humphrey Wanjugi Karin R. Deal Frank M. You Xiangyang Xu Yong Q. Gu Ming-Cheng Luo Olin D. Anderson Agnes P. Chan Pablo Rabinowicz Katrien M. Devos Jan Dvorak 《PloS one》2013,8(1)
Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands “gene insulae” to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes. 相似文献
85.
Jacqueline M. Chaparro Dayakar V. Badri Matthew G. Bakker Akifumi Sugiyama Daniel K. Manter Jorge M. Vivanco 《PloS one》2013,8(2)
Plant roots constantly secrete compounds into the soil to interact with neighboring organisms presumably to gain certain functional advantages at different stages of development. Accordingly, it has been hypothesized that the phytochemical composition present in the root exudates changes over the course of the lifespan of a plant. Here, root exudates of in vitro grown Arabidopsis plants were collected at different developmental stages and analyzed using GC-MS. Principle component analysis revealed that the composition of root exudates varied at each developmental stage. Cumulative secretion levels of sugars and sugar alcohols were higher in early time points and decreased through development. In contrast, the cumulative secretion levels of amino acids and phenolics increased over time. The expression in roots of genes involved in biosynthesis and transportation of compounds represented in the root exudates were consistent with patterns of root exudation. Correlation analyses were performed of the in vitro root exudation patterns with the functional capacity of the rhizosphere microbiome to metabolize these compounds at different developmental stages of Arabidopsis grown in natural soils. Pyrosequencing of rhizosphere mRNA revealed strong correlations (p<0.05) between microbial functional genes involved in the metabolism of carbohydrates, amino acids and secondary metabolites with the corresponding compounds released by the roots at particular stages of plant development. In summary, our results suggest that the root exudation process of phytochemicals follows a developmental pattern that is genetically programmed. 相似文献
86.
Jerome Mauris Flavio Mantelli Ashley M. Woodward Ziyhi Cao Carolyn R. Bertozzi Noorjahan Panjwani Kamil Godula Pablo Argüeso 《PloS one》2013,8(8)
Background
Interaction of transmembrane mucins with the multivalent carbohydrate-binding protein galectin-3 is critical to maintaining the integrity of the ocular surface epithelial glycocalyx. This study aimed to determine whether disruption of galectin-3 multimerization and insertion of synthetic glycopolymers in the plasma membrane could be used to modulate glycocalyx barrier function in corneal epithelial cells.Methodology/Principal Findings
Abrogation of galectin-3 biosynthesis in multilayered cultures of human corneal epithelial cells using siRNA, and in galectin-3 null mice, resulted in significant loss of corneal barrier function, as indicated by increased permeability to the rose bengal diagnostic dye. Addition of β-lactose, a competitive carbohydrate inhibitor of galectin-3 binding activity, to the cell culture system, transiently disrupted barrier function. In these experiments, treatment with a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, but not full-length galectin-3, prevented the recovery of barrier function to basal levels. As determined by fluorescence microscopy, both cellobiose- and lactose-containing glycopolymers incorporated into apical membranes of corneal epithelial cells, independently of the chain length distribution of the densely glycosylated, polymeric backbones. Membrane incorporation of cellobiose glycopolymers impaired barrier function in corneal epithelial cells, contrary to their lactose-containing counterparts, which bound to galectin-3 in pull-down assays.Conclusions/Significance
These results indicate that galectin-3 multimerization and surface recognition of lactosyl residues is required to maintain glycocalyx barrier function at the ocular surface. Transient modification of galectin-3 binding could be therapeutically used to enhance the efficiency of topical drug delivery. 相似文献87.
Daniel H. Lopez Maria A. Fiol-deRoque Maria A. Noguera-Salvà Silvia Terés Federica Campana Stefano Piotto José A. Castro Raheem J. Mohaibes Pablo V. Escribá Xavier Busquets 《PloS one》2013,8(8)
Background
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a family of COX1 and COX2 inhibitors used to reduce the synthesis of pro-inflammatory mediators. In addition, inflammation often leads to a harmful generation of nitric oxide. Efforts are being done in discovering safer NSAIDs molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators and nitric oxide to reduce the side effects associated with long term therapies.Methodology/Principal Findings
The analogue of arachidonic acid (AA), 2-hydroxy-arachidonic acid (2OAA), was designed to inhibit the activities of COX1 and COX2 and it was predicted to have similar binding energies as AA for the catalytic sites of COX1 and COX2. The interaction of AA and 2OAA with COX1 and COX2 was investigated calculating the free energy of binding and the Fukui function. Toxicity was determined in mouse microglial BV-2 cells. COX1 and COX2 (PGH2 production) activities were measured in vitro. COX1 and COX2 expression in human macrophage-like U937 cells were carried out by Western blot, immunocytochemistry and RT-PCR analysis. NO production (Griess method) and iNOS (Western blot) were determined in mouse microglial BV-2 cells. The comparative efficacy of 2OAA, ibuprofen and cortisone in lowering TNF-α serum levels was determined in C57BL6/J mice challenged with LPS. We show that the presence of the –OH group reduces the likelihood of 2OAA being subjected to H* abstraction in COX, without altering significantly the free energy of binding. The 2OAA inhibited COX1 and COX2 activities and the expression of COX2 in human U937 derived macrophages challenged with LPS. In addition, 2OAA inhibited iNOS expression and the production of NO in BV-2 microglial cells. Finally, oral administration of 2OAA decreased the plasma TNF-α levels in vivo.Conclusion/Significance
These findings demonstrate the potential of 2OAA as a NSAID. 相似文献88.
Pablo García-Gómez Abdellatif Bahaji Samuel Gámez-Arcas Francisco José Muñoz Ángela María Sánchez-López Goizeder Almagro Edurne Baroja-Fernández Kinia Ameztoy Nuria De Diego Lydia Ugena Lukáš Spíchal Karel Doležal Mohammad-Reza Hajirezaei Luis C. Romero Irene García Javier Pozueta-Romero 《Plant, cell & environment》2020,43(10):2551-2570
89.
Darío C. Colautti Leandro Miranda Mariano Gonzalez-Castro Vanina Villanova Carlos A. Strüssmann Miguel Mancini Tomas Maiztegui Gustavo Berasain Ricardo Hattori Fabian Grosman Pablo Sanzano Ismael Lozano Sabina L. Vegh Victor Salinas Omar Del Ponti Pamela del Fresno Priscila Minotti Yoji Yamamoto Claudio R. M. Baigún 《Journal of fish biology》2020,96(1):202-216
In South America, the order Atheriniformes includes the monophyletic genus Odontesthes with 20 species that inhabit freshwater, estuarine and coastal environments. Pejerrey Odontesthes argentinensis is widely distributed in coastal and estuarine areas of the Atlantic Ocean and is known to foray into estuaries of river systems, particularly in conditions of elevated salinity. However, to our knowledge, a landlocked self-sustaining population has never been recorded. In this study, we examined the pejerrey population of Salada de Pedro Luro Lake (south-east of Buenos Aires Province, Argentina) to clarify its taxonomic identity. An integrative taxonomic analysis based on traditional meristic, landmark-based morphometrics and genetic techniques suggests that the Salada de Pedro Luro pejerrey population represents a novel case of physiological and morphological adaptation of a marine pejerrey species to a landlocked environment and emphasises the environmental plasticity of this group of fishes. 相似文献
90.
Ifey Alio Mirja Gudzuhn Pablo Pérez García Dominik Danso Marie Charlotte Schoelmerich Uwe Mamat Ulrich E. Schaible J?rg Steinmann Daniel Yero Isidre Gibert Thomas A. Kohl Stefan Niemann Matthias I. Gr?schel Johanna Haerdter Thomas Hackl Christel Vollstedt Mechthild B?meke Richard Egelkamp Rolf Daniel Anja Poehlein Wolfgang R. Streit 《Applied and environmental microbiology》2020,86(24)