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   4552篇
  免费   417篇
  国内免费   1篇
  2023年   21篇
  2022年   48篇
  2021年   83篇
  2020年   58篇
  2019年   66篇
  2018年   66篇
  2017年   64篇
  2016年   132篇
  2015年   214篇
  2014年   231篇
  2013年   318篇
  2012年   419篇
  2011年   368篇
  2010年   247篇
  2009年   241篇
  2008年   299篇
  2007年   308篇
  2006年   299篇
  2005年   291篇
  2004年   272篇
  2003年   251篇
  2002年   276篇
  2001年   42篇
  2000年   23篇
  1999年   45篇
  1998年   72篇
  1997年   39篇
  1996年   32篇
  1995年   36篇
  1994年   23篇
  1993年   25篇
  1992年   16篇
  1991年   7篇
  1990年   4篇
  1989年   3篇
  1988年   4篇
  1987年   2篇
  1986年   2篇
  1984年   1篇
  1982年   2篇
  1981年   1篇
  1978年   1篇
  1974年   4篇
  1972年   3篇
  1971年   5篇
  1970年   1篇
  1969年   2篇
  1967年   1篇
  1965年   1篇
  1923年   1篇
排序方式: 共有4970条查询结果,搜索用时 31 毫秒
941.

Background

The prevalence of back pain is constantly increasing and a public health problem of high priority. In Austria there is a lack of empirical evidence for the development of back pain and its related factors. The present study aims to investigate trends in the prevalence of back pain across different subpopulations (sex, age, obesity).

Methods

A secondary data analysis based on five nationally representative cross-sectional health surveys (1973–2007) was carried out. Face-to-face interviews were conducted in private homes in Austria. Subjects aged 20 years and older were included in the study sample (n = 178,818). Obesity was defined as BMI≥30 kg/m2 and adjusted for self-report bias. Back pain was measured as the self-reported presence of the disorder.

Results

The age-standardized prevalence of back pain was 32.9% in 2007; it was higher among women than men (p<0.001), higher in older than younger subjects (p<0.001) and higher in obese than non-obese individuals (p<0.001). During the investigation period the absolute change in the prevalence of back pain was +19.4%. Among all subpopulations the prevalence steadily increased. Obese men showed the highest increase of and the greatest risk for back pain.

Conclusion

These results help to understand the development of back pain in Austria and can be used to plan controlled promotion programs. Further monitoring is recommended in order to control risk groups and plan target group-specific prevention strategies. In Austria particular emphasis should be on obese individuals. We recommend conducting prospective studies to confirm our results and investigate causal relationships.  相似文献   
942.
The cystic fibrosis transmembrane regulator (CFTR) is a cyclic-AMP dependent chloride channel expressed at the apical surface of epithelial cells lining various organs such as the respiratory tract. Defective processing and functioning of this protein caused by mutations in the CFTR gene results in loss of ionic balance, defective mucus clearance, increased proliferation of biofilms and inflammation of human airways observed in cystic fibrosis (CF) patients. The process by which CFTR folds and matures under the influence of various chaperones in the secretory pathway remains incompletely understood. Recently, calumenin, a secretory protein, belonging to the CREC family of low affinity calcium binding proteins has been identified as a putative CFTR chaperone whose biophysical properties and functions remain uncharacterized. We compared hydropathy, instability, charge, unfoldability, disorder and aggregation propensity of calumenin and other CREC family members with CFTR associated chaperones and calcium binding proteins, wild-type and mutant CFTR proteins and intrinsically disordered proteins (IDPs). We observed that calumenin, along with other CREC proteins, was significantly more charged and less folded compared to CFTR associated chaperones. Moreover like IDPs, calumenin and other CREC proteins were found to be less hydrophobic and aggregation prone. Phylogenetic analysis revealed a close link between calumenin and other CREC proteins indicating how evolution might have shaped their similar biophysical properties. Experimentally, calumenin was observed to significantly reduce F508del-CFTR aggregation in a manner similar to AavLEA1, a well-characterized IDP. Fluorescence microscopy based imaging analysis also revealed altered trafficking of calumenin in bronchial cells expressing F508del-CFTR, indicating its direct role in the pathophysiology of CF. In conclusion, calumenin is characterized as a charged protein exhibiting close similarity with IDPs and is hypothesized to regulate F508del-CFTR folding by electrostatic effects. This work provides useful insights for designing optimized synthetic structural correctors of CFTR mutant proteins in the future.  相似文献   
943.
944.
Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3 Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8–9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occuring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo.  相似文献   
945.
We propose using the surface of pine trees needles to biomonitor the bioaerosol emissions at a composting plant. Measurements were based on 16S rRNA gene copy numbers of Saccharopolyspora rectivirgula, a bioindicator of composting plant emissions. A sampling plan was established based on 29 samples around the emission source. The abundance of 16S rRNA gene copies of S. rectivirgula per gram of Pinus halepensis needles varied from 104 to 102 as a function of the distance. The signal reached the background level at distances around the composting plant ranging from 2 km to more than 5.4 km, depending on the local topography and average wind directions. From these values, the impacted area around the source of bioaerosols was mapped.  相似文献   
946.
Advanced MR imaging methods have an essential role in classification, grading, follow-up and therapeutic management in patients with brain tumors. With the introduction of new therapeutic options, the challenge for better tissue characterization and diagnosis increase, calling for new reliable non-invasive imaging methods. In the current study we evaluated the added value of a combined protocol of blood oxygen level dependent (BOLD) imaging during hyperoxic challenge (termed hemodynamic response imaging (HRI)) in an orthotopic mouse model for glioblastoma under anti-angiogenic treatment with B20-4.1.1, an anti-VEGF antibody. In glioblastoma tumors, the elevated HRI indicated progressive angiogenesis as further confirmed by histology. In the current glioblastoma model, B20-treatment caused delayed tumor progression with no significant changes in HRI yet with slightly reduced tumor vascularity as indicated by histology. Furthermore, fewer apoptotic cells and higher proliferation index were detected in the B20-treated tumors compared to control-treated tumors. In conclusion, HRI provides an easy, safe and contrast agent free method for the assessment of the brain hemodynamic function, an additionally important clinical information.  相似文献   
947.
In recent years, more attention has been paid to exposure of the general population to household products. In order to assess exposure, it is necessary to generate exposure data. For this reason, a preliminary study of dishwashing liquid contact on Brest university students was performed. Dishwashing liquid is frequently used and when it is improperly mixed it can liberate harmful molecules. As for university students, they may have a repetitive contact with dishwashing liquid during their academic studies. Relevant parameters as frequency of dishwashing, duration, and amount of dishwashing liquid were assessed from questionnaires and laboratory tests. Tests revealed that overall no difference between the sexes and the type of residential household on dishwashing was present on this population. Amount of washed items and duration was significantly correlated, which could seem logical but remarkable considering the lack of correlation between other parameters. Values of 1.39 and 58.8 μg/kg bw/day for the 95th percentile of dermal and inhalation probabilistic exposure were found, respectively. Dermal exposure coincides with deterministic published data. In the case of inhalation exposure no published data are available. Higher inhalation exposure value may show that dermal exposure is diminished by high dilution of dishwashing liquid in water.  相似文献   
948.
949.
950.
Despite the availability of therapy and vaccine, tuberculosis (TB) remains one of the most deadly and widespread bacterial infections in the world. Since several decades, the sudden burst of multi- and extensively-drug resistant strains is a serious threat for the control of tuberculosis. Therefore, it is essential to identify new targets and pathways critical for the causative agent of the tuberculosis, Mycobacterium tuberculosis (Mtb) and to search for novel chemicals that could become TB drugs. One approach is to set up methods suitable for the genetic and chemical screens of large scale libraries enabling the search of a needle in a haystack. To this end, we developed a phenotypic assay relying on the detection of fluorescently labeled Mtb within fluorescently labeled host cells using automated confocal microscopy. This in vitro assay allows an image based quantification of the colonization process of Mtb into the host and was optimized for the 384-well microplate format, which is proper for screens of siRNA-, chemical compound- or Mtb mutant-libraries. The images are then processed for multiparametric analysis, which provides read out inferring on the pathogenesis of Mtb within host cells.  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