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   1544篇
  免费   120篇
  2023年   11篇
  2022年   17篇
  2021年   18篇
  2020年   26篇
  2019年   18篇
  2018年   22篇
  2017年   29篇
  2016年   39篇
  2015年   51篇
  2014年   75篇
  2013年   88篇
  2012年   115篇
  2011年   115篇
  2010年   72篇
  2009年   53篇
  2008年   74篇
  2007年   82篇
  2006年   89篇
  2005年   75篇
  2004年   68篇
  2003年   55篇
  2002年   57篇
  2001年   23篇
  2000年   15篇
  1999年   16篇
  1998年   21篇
  1997年   11篇
  1996年   16篇
  1995年   14篇
  1994年   12篇
  1993年   12篇
  1992年   12篇
  1991年   10篇
  1990年   10篇
  1989年   11篇
  1988年   9篇
  1986年   7篇
  1985年   10篇
  1984年   11篇
  1983年   11篇
  1982年   10篇
  1981年   8篇
  1973年   8篇
  1972年   13篇
  1971年   7篇
  1970年   7篇
  1969年   9篇
  1968年   7篇
  1967年   6篇
  1881年   8篇
排序方式: 共有1664条查询结果,搜索用时 46 毫秒
51.
Over the last decades, post‐illumination bursts (PIBs) of isoprene, acetaldehyde and green leaf volatiles (GLVs) following rapid light‐to‐dark transitions have been reported for a variety of different plant species. However, the mechanisms triggering their release still remain unclear. Here we measured PIBs of isoprene‐emitting (IE) and isoprene non‐emitting (NE) grey poplar plants grown under different climate scenarios (ambient control and three scenarios with elevated CO2 concentrations: elevated control, periodic heat and temperature stress, chronic heat and temperature stress, followed by recovery periods). PIBs of isoprene were unaffected by elevated CO2 and heat and drought stress in IE, while they were absent in NE plants. On the other hand, PIBs of acetaldehyde and also GLVs were strongly reduced in stress‐affected plants of all genotypes. After recovery from stress, distinct differences in PIB emissions in both genotypes confirmed different precursor pools for acetaldehyde and GLV emissions. Changes in PIBs of GLVs, almost absent in stressed plants and enhanced after recovery, could be mainly attributed to changes in lipoxygenase activity. Our results indicate that acetaldehyde PIBs, which recovered only partly, derive from a new mechanism in which acetaldehyde is produced from methylerythritol phosphate pathway intermediates, driven by deoxyxylulose phosphate synthase activity.  相似文献   
52.

Background

In recent epidemiological models, immunity is incorporated as a simplified value that determines the capacity of an individual to become infected or to transmit the disease. Moreover, the quality of the immune response determines the chances of infection and the length of time an individual is capable to infect others. We present a model that incorporates individuals’ immune responses to, further, examine the role of the collective immune response of individuals in a population during an infectious outbreak.

Methods

We constructed a contagion model that incorporates the collective immune response of individuals represented by the superposition of individual immune responses (PIR). Multiple probability distributions are used to represent the immunocompetence of different age groups, thereby modeling the concept of Population Immune Response (PIR). Multiple experiments were conducted in which the population is divided in different age groups for which each group has a unique immune response quality and thus a different length for its immune periods. Finally, we explored the effects of implementing different vaccination strategies in the population.

Results

The experiments displayed important variations in the outbreak dynamics as a consequence of incorporating PIR in homogeneous and mixed populations. The experiments showed that individuals with weak immune responses and those who are immune to the pathogen play a significant role in shaping the outbreak dynamics. Finally, after implementing different vaccination strategies, the results suggest that if vaccination resources are limited, the vaccination should be targeted towards individuals that spread the disease for a longer period of time.

Conclusions

Our results suggest that it is essential for the public health establishment to increase their understanding of the characteristics of regional demographics that could impact the quality of the immune response of the individuals. The results indicate that it is necessary to further investigate mitigation strategies to limit the capacity to transmit the disease by individuals that spread the pathogen for extended periods of time. Ultimately, this study suggests that it is crucial for public health researchers to identify appropriate targeted vaccination regimes and to explore the link between PIR and outbreak dynamics to improve the monitoring and mitigating efforts of ongoing and future epidemics.
  相似文献   
53.

Background

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic, hereditary, small vessel disease of the brain causing stroke and vascular dementia in adults. CADASIL has previously been shown to be caused by varying mutations in the NOTCH3 gene. The disorder is often misdiagnosed due to its significant clinical heterogeneic manifestation with familial hemiplegic migraine and several ataxia disorders as well as the location of the currently identified causative mutations. The aim of this study was to develop a new, comprehensive and efficient single assay strategy for complete molecular diagnosis of NOTCH3 mutations through the use of a custom next-generation sequencing (NGS) panel for improved routine clinical molecular diagnostic testing.

Results

Our custom NGS panel identified nine genetic variants in NOTCH3 (p.D139V, p.C183R, p.R332C, p.Y465C, p.C597W, p.R607H, p.E813E, p.C977G and p.Y1106C). Six mutations were stereotypical CADASIL mutations leading to an odd number of cysteine residues in one of the 34 NOTCH3 gene epidermal growth factor (EGF)-like repeats, including three new typical cysteine mutations identified in exon 11 (p.C597W; c.1791C>G); exon 18 (p.C977G; c.2929T>G) and exon 20 (p.Y1106C; c.3317A>G). Interestingly, a novel missense mutation in the CACNA1A gene was also identified in one CADASIL patient. All variants identified (novel and known) were further investigated using in silico bioinformatic analyses and confirmed through Sanger sequencing.

Conclusions

NGS provides an improved and effective methodology for the diagnosis of CADASIL. The NGS approach reduced time and cost for comprehensive genetic diagnosis, placing genetic diagnostic testing within reach of more patients.
  相似文献   
54.
Allicin, a broad‐spectrum antimicrobial agent from garlic, disrupts thiol and redox homeostasis, proteostasis, and cell membrane integrity. Since medicine demands antimicrobials with so far unexploited mechanisms, allicin is a promising lead structure. While progress is being made in unraveling its mode of action, little is known on bacterial adaptation strategies. Some isolates of Pseudomonas aeruginosa and Escherichia coli withstand exposure to high allicin concentrations due to as yet unknown mechanisms. To elucidate resistance and sensitivity‐conferring cellular processes, the acute proteomic responses of a resistant P. aeruginosa strain and the sensitive species Bacillus subtilis are compared to the published proteomic response of E. coli to allicin treatment. The cellular defense strategies share functional features: proteins involved in translation and maintenance of protein quality, redox homeostasis, and cell envelope modification are upregulated. In both Gram‐negative species, protein synthesis of the majority of proteins is downregulated while the Gram‐positive B. subtilis responded by upregulation of multiple regulons. A comparison of the B. subtilis proteomic response to a library of responses to antibiotic treatment reveals 30 proteins specifically upregulated by allicin. Upregulated oxidative stress proteins are shared with nitrofurantoin and diamide. Microscopy‐based assays further indicate that in B. subtilis cell wall integrity is impaired.  相似文献   
55.
We used fluorescently labeled phalloidin to examine the subumbrellar musculature of the scyphozoan jellyfish Aurelia aurita in a developmental series from ephyra to adult medusa. In the ephyra, the swim musculature includes a disc‐like sheet of circular muscle, in addition to two radial bands of muscle in each of the eight ephyral arms. The radial muscle bands join with the circular muscle, and both circular and radial muscle act together during each swim contraction. As the ephyra grows into a juvenile medusa, arms tissue is resorbed as the bell tissue grows outward, so eventually, the ephyral arms disappear. During this process, the circular muscle disc also grows outward and the radial muscle bands of the arms also disappear. At this time, a marginal gap appears at the bell margin, which is devoid of circular muscle cells, but has a loose arrangement of radial muscle fibers. This marginal gap is preserved as the medusa grows, and contributes to the floppy nature of the bell margin. Radial distortions in the circular muscle layer involve muscle fibers that run in random directions, with a primarily radial orientation. These are believed to be remnants of the radial muscle of the ephyral arms, and the distortions decrease in number and extent as the medusa grows. Since the mechanics of swimming changes from drag‐based paddling in the ephyra to marginal rowing in the adult medusa, the development of the marginal gap and the presence of radial distortions should be considered in terms of this mechanical transition.  相似文献   
56.
57.
The biopharmaceutical industry gains enormous flexibility in production processes by using sterilized preassembled single-use devices. Gamma irradiation is an established sterilization technology that may be restricted in the future by the availability of 60Co as irradiation source and irradiation capacities. X-ray technology is considered an alternative type of radiation for sterilizing SU equipment. In the context of extractables and leachables—one concern connected with the use of single-use process equipment—the effect of X-ray irradiation on the extractables profile of the materials needs to be compared to established gamma irradiation to qualify this alternative technology. An approach is presented to obtain robust and comprehensive extractables data for materials used in SU devices after sterilization either using X-ray or gamma irradiation. A careful selection of the test items and the test design allows a one-to-one comparison of data obtained from a combination of orthogonal analytical techniques. The extractables of a modern SU film material and the copolyester Tritan™ are evaluated. The data presented allow a risk evaluation on the safety of this new sterilization modality for biopharmaceutical applications. It is demonstrated that the extractables profile of a polymer is not affected by the type of irradiation used for sterilization.  相似文献   
58.
A new class of galactooligosaccharides has been identified from the terrestrial cyanobacterium Nostoc commune by MS and NMR techniques. These consist of beta-D-galactofuranosyl-(1-->6)-[beta-D-galactofuranosyl-(1-->6)]n-beta-d-1,4-anhydrogalactitols with n ranging from 2 to 8, corresponding to compounds designated 1 through 7. In total these saccharides amounted to approximately 0.35% of the dry thallus of N. commune, while in several other cyanobacteria they were not detected. Possibly they play some role in protection from damage by heat and desiccation as suggested by experiments with heterologous systems. For example, phosphoglucomutase (EC 2.7.5.1) from rabbit muscle was protected against heat inactivation by these oligosaccharides, and alpha-amylase (EC 3.2.1.1) from porcine pancreas by the oligosaccharides 6 and 7. The homologues of lower molecular mass, however, enhanced heat sensitivity of alpha-amylase. The viability of Escherichia coli was completely abolished by desiccation, whereas in the presence of 4 survival rates were approximately 50% of controls not subjected to desiccation. The newly identified saccharides are compared with known galactofuranose-based oligo- and polysaccharides and possible biological functions of them are discussed.  相似文献   
59.

Background  

The enormity of the information contained in large data sets makes it difficult to develop intuitive understanding. It would be useful to have software that allows visualization of possible correlations between properties that can be associated with a core data set. In the case of bacterial genomes, existing visualization tools focus on either global properties such as variations in composition or detailed local displays of the features that comprise the annotation. It is not easy to visualize other information in the context of this core information.  相似文献   
60.
Objective: Severe obesity is a clear indication for appropriate, effective weight loss therapy. One option is operative intervention, e.g., gastric banding. Risks of the operation and therapeutic alternatives need to be comprehensibly presented to the patient. The literature has shown that better informed consent is obtained using information presented in a multimedia/video‐based format. The current study developed and evaluated a multimedia program aimed at obtaining informed consent from obese patients before gastric banding. Research Methods and Procedure: An interactive multimedia program was developed with information about preoperative examinations, the operation itself, hospital stay, operative risks, alternative therapies, and the pathophysiology and health risks of obesity. Two groups (Group 1, n = 20, mean age 38 years, informed consent attained with conventional document information; Group 2, n = 20, mean age 37 years, informed consent attained with additional multimedia information) were interviewed regarding comprehensibility of the information presented, personal satisfaction, and anxiety levels during the informed consent process. Results: Group 2 showed significantly better (p < 0.05) understanding of the presented information and higher levels of satisfaction with the informed consent process. Anxiety levels did not significantly differ between the two groups. Discussion: Because patient satisfaction with the informed consent process and understanding of the presented information significantly improved, the multimedia program clearly benefits both surgeons and patients. Personal contact from the surgeon remains essential. High volumes of information presented in multimedia format do not alleviate patient anxiety, and personal contact may be beneficial.  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