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   1340篇
  免费   102篇
  2023年   5篇
  2022年   6篇
  2021年   14篇
  2020年   6篇
  2019年   25篇
  2018年   32篇
  2017年   26篇
  2016年   45篇
  2015年   83篇
  2014年   58篇
  2013年   105篇
  2012年   114篇
  2011年   98篇
  2010年   84篇
  2009年   64篇
  2008年   82篇
  2007年   74篇
  2006年   99篇
  2005年   61篇
  2004年   71篇
  2003年   55篇
  2002年   60篇
  2001年   24篇
  2000年   21篇
  1999年   8篇
  1998年   14篇
  1997年   10篇
  1996年   6篇
  1995年   12篇
  1994年   14篇
  1993年   9篇
  1992年   9篇
  1991年   9篇
  1990年   5篇
  1989年   2篇
  1988年   2篇
  1987年   5篇
  1986年   4篇
  1985年   3篇
  1983年   2篇
  1981年   2篇
  1973年   1篇
  1972年   1篇
  1971年   1篇
  1970年   2篇
  1969年   1篇
  1968年   1篇
  1952年   1篇
  1935年   1篇
  1934年   1篇
排序方式: 共有1442条查询结果,搜索用时 15 毫秒
91.
As marine systems are threatened by increasing human impacts, mechanisms to maintain biodiversity and ecosystem functions and services are needed. Protecting areas of conservation importance may serve as a proxy for maintaining these functions, while also facilitating efficient use and management of limited resources. Biodiversity hotspots have been used as surrogates for spatial conservation importance; however, as many protected areas have been established opportunistically and under differing criteria, it is unclear how well they actually protect hotspots. We evaluated how well the current protected area network and priority areas selected through previous systematic conservation planning exercises preserve biodiversity hotspots in the Gulf of California, Mexico. We also determined spatial congruence between biodiversity hotspots based on different criteria, which may determine their ability to be used as surrogates for each other. We focus on the Gulf of California because it is a megadiverse system where limited information regarding species diversity and distribution has constrained development of strategies for conservation and management. We developed a species occurrence database and identified biodiversity hotspots using four different criteria: species richness, rarity, endemism, and threatened species. We interpolated species occurrence, while accounting for heterogeneous sampling efforts. We then assessed overlap of hotspots with existing protected areas and priority areas, and between hotspots derived by distinct criteria. We gathered 286,533 occurrence records belonging to 12,105 unique species, including 6388 species identified as rare, 642 as endemic, and 386 as threatened. We found that biodiversity hotspots showed little spatial overlap with areas currently under protection and previously identified priority areas. Our results highlight the importance of distinct spatial areas of biodiversity and suggest that different ecological mechanisms sustain different aspects of diversity and multiple criteria should be used when defining conservation areas.  相似文献   
92.
Bioprocess and Biosystems Engineering - Conventional biosurfactants have high production costs. Therefore, the use of low-cost carbon sources for their production is attractive for industry. The...  相似文献   
93.
Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism. Although loss of presenilin 1 function has been reported to impair lysosomal function and prevent autophagy flux, the detailed mechanism leading to autophagy dysfunction in AD remains to be elucidated. The resemblance between pathological hallmarks of AD and Niemann-Pick Type C disease, including endosome-lysosome abnormalities and impaired autophagy, suggests cholesterol accumulation as a common link. Using a mouse model of AD (APP-PSEN1-SREBF2 mice), expressing chimeric mouse-human amyloid precursor protein with the familial Alzheimer Swedish mutation (APP695swe) and mutant presenilin 1 (PSEN1-dE9), together with a dominant-positive, truncated and active form of SREBF2/SREBP2 (sterol regulatory element binding factor 2), we demonstrated that high brain cholesterol enhanced autophagosome formation, but disrupted its fusion with endosomal-lysosomal vesicles. The combination of these alterations resulted in impaired degradation of Aβ and endogenous MAPT (microtubule associated protein tau), and stimulated autophagy-dependent Aβ secretion. Exacerbated Aβ-induced oxidative stress in APP-PSEN1-SREBF2 mice, due to cholesterol-mediated depletion of mitochondrial glutathione/mGSH, is critical for autophagy induction. In agreement, in vivo mitochondrial GSH recovery with GSH ethyl ester, inhibited autophagosome synthesis by preventing the oxidative inhibition of ATG4B deconjugation activity exerted by Aβ. Moreover, cholesterol-enrichment within the endosomes-lysosomes modified the levels and membrane distribution of RAB7A and SNAP receptors (SNAREs), which affected its fusogenic ability. Accordingly, in vivo treatment with 2-hydroxypropyl-β-cyclodextrin completely rescued these alterations, making it a potential therapeutic tool for AD.  相似文献   
94.
Chromosomal abnormalities are detected in 20–30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions. Differential methylation analysis between patients and controls allowed us to identify abnormalities in DNA methylation, including hypermethylation of specific genes and large genome regions with aberrant DNA methylation. Unsupervised hierarchical cluster analysis identified two main clusters that associated with the clinical, biological, and genetic features of patients. Group 1 was enriched in patients with adverse clinical and biological characteristics and poorer overall and progression-free survival. In addition, significant differences in DNA methylation were observed between patients with low risk and intermediate/high risk karyotypes and between TET2 mutant and wild type patients. Taken together, our results demonstrate that altered DNA methylation patterns reflect the CMML disease state and allow to identify patient groups with distinct clinical features.  相似文献   
95.
Investment in anti-herbivore defence in tree species has been one of the priority research topics in plant terrestrial ecology during the last decades. However, despite considerable experimental effort, interspecific differences in the ontogenetic trends in the investment in defence are still a matter of debate, as to date experimental evidence is contradictory. In the present work, insect herbivory levels were measured in seedlings and mature trees of four co-occurring Mediterranean Quercus species with differing leaf life spans, as well as several leaf characteristics that can determine herbivore preference. The measured leaf traits included nitrogen (N), fibre (cellulose, hemicellulose and lignin), total phenolic contents, leaf mass per unit area (LMA) and leaf thickness. The leaves of seedlings had a lower LMA and leaf thickness and lower concentrations of N and cellulose, but higher concentrations of lignin and phenols than those of mature trees. However, the loss of leaf area tended to be more severe for seedlings than for mature trees, although the differences were only significant for deciduous species. This constitutes a confirmation of the strong effects of physical traits on herbivore preferences. The greater resource limitations for defensive mechanisms in seedlings with respect to mature trees would explain that at intraspecific level we do observe a compromise between chemical and physical defences. As a result, seedlings rely on chemical rather than on physical defences.  相似文献   
96.
Ethylene favors carposporogenesis in the red seaweed Grateloupia imbricata. Analyses of cystocarp development in vitro in thalli treated with ethylene suggest an interconnection between polyamine and ethylene biosynthesis pathways. Yet, little is known about molecular mechanisms underlying carposporogenesis. Here, we used droplet digital PCR to analyze genes encoding enzymes related to polyamine (Spermidine [Spd] synthase) and ethylene (ACC synthase) synthesis; a pivotal compound of both pathways (S‐adenosyl methionine synthase, SAMS); the gene that encodes amine oxidase, which is involved in polyamine degradation, and a candidate gene involved in seaweed reproduction (ornithine decarboxylase, ODC). In addition, we analyzed genes encoding proteins related to stress and reactive oxygen species, ascorbate peroxidase (APX), cytochrome P450 and WD 40. We characterized gene expression in fertilized and fertile thalli from G. imbricata that were exposed to ethylene for 15 min at two time points after treatment (1 and 7 d). The differential gene expression of SAMS, Spd synthase, ACC synthase, and cytochrome P450 was related to disclosure and development of cystocarps in fertilized thalli that transitioned from having no visible cystocarps at 1 d to developing cystocarps at 7 d. Likewise, cytochrome P450 was associated with cystocarp disclosure and maturation. In addition, amine oxidase and APX were involved in fine‐tuning polyamine and reactive oxygen species during carposporogenesis, respectively, whereas WD 40 did so in relation to ethylene signaling. Expression of the candidate gene ODC was increased when cystocarps were not visible (fertilized thalli, 1d), as previously described. This analysis suggests developmental stage‐specific roles for these genes during carposporogenesis.  相似文献   
97.
Despite secular trends in some countries, prestige-based authority in the form of religious leadership remains hugely influential in the everyday lives of millions of people around the world. Here, the costs and benefits of religious leadership are explored in an urban setting in northeastern Brazil. An economic game, within-group cooperation questionnaires, and social network analyses were carried out among adherents of an Afro-Brazilian religion. Results reveal that leaders display high levels of religious commitment and disproportionally provide cooperative services to group members. On the other hand, initiates cooperate less than leaders but do not differ in levels of received cooperation or social cohesion measures. This may indicate some level of exploitation or free-riding. Demographic and group variables also appear to play an important role in the degree of social cohesion a group achieves. These findings are discussed in the context of non-Western urban settings where religious leadership may represent both an alternative to social advancement and a crucial source of material aid, social support, and a strong sense of community.  相似文献   
98.

Background

Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA.

Methods

A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay.

Results

Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment.

Conclusions

The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up.

Trial Registration

ClinicalTrials.gov NCT01335087  相似文献   
99.

Background

Venous thromboembolism (VTE) is a common disease where known genetic risk factors explain only a small portion of the genetic variance. Then, the analysis of intermediate phenotypes, such as thrombin generation assay, can be used to identify novel genetic risk factors that contribute to VTE.

Objectives

To investigate the genetic basis of distinct quantitative phenotypes of thrombin generation and its relationship to the risk of VTE.

Patients/Methods

Lag time, thrombin peak and endogenous thrombin potential (ETP) were measured in the families of the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT-2) Project. This sample consisted of 935 individuals in 35 extended families selected through a proband with idiopathic thrombophilia. We performed also genome wide association studies (GWAS) with thrombin generation phenotypes.

Results

The results showed that 67% of the variation in the risk of VTE is attributable to genetic factors. The heritabilities of lag time, thrombin peak and ETP were 49%, 54% and 52%, respectively. More importantly, we demonstrated also the existence of positive genetic correlations between thrombin peak or ETP and the risk of VTE. Moreover, the major genetic determinant of thrombin generation was the F2 gene. However, other suggestive signals were observed.

Conclusions

The thrombin generation phenotypes are strongly genetically determined. The thrombin peak and ETP are significantly genetically correlated with the risk of VTE. In addition, F2 was identified as a major determinant of thrombin generation. We reported suggestive signals that might increase our knowledge to explain the variability of this important phenotype. Validation and functional studies are required to confirm GWAS results.  相似文献   
100.
Plant biomass offers a renewable and environmentally favorable source of sugars that can be converted to different chemicals, second-generation ethanol, and other liquid fuels. Cellulose makes up approximately 45 % of the dry weight of lignocellulosic biomass. Prior to the enzymatic hydrolysis of cellulose, lignin and hemicellulose must be structurally altered or removed, at least in part, by chemical and/or physical pretreatments. However, the high cost and low efficiency of the enzymatic hydrolysis prevent the process from being economically competitive. For this reason, it is necessary to find enzymes suitable for this type of process, with higher specific activities and greater efficiency. Members of the Bacillus and Paenibacillus genera have been traditionally used for the production of many enzymes for industrial applications. Cellulases produced by both genera have shown activity on soluble and crystalline cellulose and high thermostability and/or activity over a wide pH spectrum. In this review, the most recent information about the characterization of cellulolytic enzymes obtained from new strains of the Bacillus and Paenibacillus genera are reviewed. We focused on the variety of isoenzymes produced by these cellulolytic strains, their optimal production and reaction conditions, and their kinetic parameters and biotechnological potential.  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