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   4282篇
  免费   288篇
  国内免费   6篇
  2024年   1篇
  2023年   15篇
  2022年   8篇
  2021年   75篇
  2020年   48篇
  2019年   80篇
  2018年   113篇
  2017年   104篇
  2016年   168篇
  2015年   212篇
  2014年   273篇
  2013年   315篇
  2012年   384篇
  2011年   392篇
  2010年   209篇
  2009年   208篇
  2008年   306篇
  2007年   252篇
  2006年   191篇
  2005年   187篇
  2004年   181篇
  2003年   185篇
  2002年   139篇
  2001年   125篇
  2000年   107篇
  1999年   76篇
  1998年   34篇
  1997年   19篇
  1996年   28篇
  1995年   17篇
  1994年   13篇
  1993年   12篇
  1992年   26篇
  1991年   25篇
  1990年   10篇
  1989年   14篇
  1988年   8篇
  1987年   3篇
  1986年   2篇
  1985年   3篇
  1984年   2篇
  1979年   1篇
  1975年   1篇
  1967年   1篇
  1966年   1篇
  1965年   1篇
  1963年   1篇
排序方式: 共有4576条查询结果,搜索用时 15 毫秒
81.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS); its cause is unknown. To understand the pathogenesis of MS, researchers often use the experimental autoimmune encephalomyelitis (EAE) mouse model. Here, the aim is to build a proteome map of the biological changes that occur during MS at the major onset sites—the brain and the spinal cord. Quantitative proteome profiling is performed in five specific brain regions and the spinal cord of EAE and healthy mice with high‐resolution mass spectrometry based on tandem mass tags. On average, 7400 proteins per region are quantified, with the most differentially expressed proteins in the spinal cord (1691), hippocampus (104), frontal cortex (83), cerebellum (63), brainstem (50), and caudate nucleus (41). Moreover, region‐specific and commonly expressed proteins in each region are identified and bioinformatics analysis is performed. Pathway analysis reveals that protein clusters resemble their functions in disease pathogenesis (i.e., by inducing inflammatory responses, immune activation, and cell–cell adhesion). In conclusion, the study provides an understanding of the pathogenesis of MS in the EAE animal model. It is expected that the comprehensive proteome map of the brain and spinal cord can be used to identify biomarkers for the pathogenesis of MS.  相似文献   
82.
This study presents a systematic modeling approach for examining the efficiency of the MEOR process based on in situ selective plugging by bacterial biopolymer production and optimization of the nutrient injection strategy to yield the maximum oil recovery. This study focuses on modeling in situ selective plugging by the bacterial biopolymer dextran that is generated by Leuconostoc mesenteroides. Bacterial growth and dextran generation were described by a stoichiometric equation and kinetic reactions using batch model simulation. Based on the parameters for permeability reduction obtained from the sandpack model, the MEOR process was implemented in a pilot-scale system that included a highly permeable thief zone in a low-permeability reservoir. The base MEOR design yielded a 61.5% improvement of the recovery factor compared to that obtained with waterflooding. The parametric simulations revealed that the recovery efficiency was influenced by the amount of dextran, as well as the distribution of dextran, and thus, the injection strategy is critical for controlling the dextran distribution. By incorporating the results from the sensitivity analysis and optimization to determine the optimal design parameters, a 36.7% improvement of the oil recovery was achieved with the optimized MEOR process in comparison with the base case.  相似文献   
83.
The study was conducted with the aim of furthering our understanding of seasonality in the population dynamics and infestation rates of the fruit fly Bactrocera spp. in sweet gourd (Cucurbita moschata) during winter and summer in 2017. We also investigated the effects of using methyl eugenol traps on fly abundance and infestation. Two fruit fly species, namely, B. cucurbitae and B. dorsalis, were present in the sweet gourd field, and we observed fluctuations in their abundance. Compared to B. dorsalis, B. cucurbitae was significantly more abundant in both winter and summer. Infestation level was found to be the highest in fields lacking methyl eugenol traps in both seasons. Fruit fly larval population per infested fruit was higher in summer than in winter. Fly abundance was significantly and positively correlated with mean temperature and rainfall but significantly and negatively correlated with light intensity. Relative humidity was insignificantly but positively correlated with fly abundance. The temperature, light intensity, relative humidity, and rainfall individually explained 48.9, 24.1, 0.8, and 1.6% of variation in fruit fly abundance, respectively. The combined effect of the weather parameters on fruit fly abundance was 75.4% and was significant predictor of fruit fly abundance.  相似文献   
84.
85.
Hahn  Kyu Ri  Kim  Woosuk  Jung  Hyo Young  Kwon  Hyun Jung  Kim  Dae Won  Hwang  In Koo  Yoon  Yeo Sung 《Neurochemical research》2022,47(4):1073-1082
Neurochemical Research - Cuprizone is commonly used to induce neuronal demyelination in mice. In the present study, we compared the cuprizone-induced demyelination in the corpus callosum and...  相似文献   
86.
Syndecans, a family of transmembrane heparansulfate proteoglycans, are known to interact through their transmembrane domains to form non-covalently linked homodimers, a process essential for their individual functions. Because all syndecan transmembrane domains are highly conserved and thus might mediate interactions between different members of the syndecan family, we investigated syndecan interactions in detail. All recombinant syndecan-2 and -4 protein variants containing the transmembrane domain formed not only sodium dodecyl sulfate (SDS)-resistant homodimers but also SDS-resistant heterodimers. Biochemical and structural data revealed that recombinant syndecan-2 and -4 formed intermolecular interactions in vitro, and the GXXXG motif in transmembrane domain mediated this interaction. When exogenously expressed in rat embryonic fibroblasts, syndecan-2 interacted with syndecan-4 and vice versa. Furthermore, bimolecular fluorescence complementation-based assay demonstrated specific hetero-molecular interactions between syndecan-2 and -4, supporting hetero-oligomer formation of syndecans in vivo. Interestingly, hetero-oligomerization significantly reduced syndecan-4-mediated cellular processes such as protein kinase Cα activation and protein kinase Cα-mediated cell adhesion as well as syndecan-2-mediated tumorigenic activities in colon cancer cells such as migration and anchorage-independent growth. Taken together, these data provide evidence that hetero-oligomerization produces distinct syndecan functions and offer insights into the underlying signaling mechanisms of syndecans.  相似文献   
87.
The phosphoinositide 3-kinase–Akt signaling pathway is essential to many biological processes, including cell proliferation, survival, metabolism, and angiogenesis, under pathophysiological conditions. Although 3-phosphoinositide–dependent kinase 1 (PDK1) is a primary activator of Akt at the plasma membrane, the optimal activation mechanism remains unclear. We report that adhesion molecule with IgG-like domain 2 (AMIGO2) is a novel scaffold protein that regulates PDK1 membrane localization and Akt activation. Loss of AMIGO2 in endothelial cells (ECs) led to apoptosis and inhibition of angiogenesis with Akt inactivation. Amino acid residues 465–474 in AMIGO2 directly bind to the PDK1 pleckstrin homology domain. A synthetic peptide containing the AMIGO2 465–474 residues abrogated the AMIGO2–PDK1 interaction and Akt activation. Moreover, it effectively suppressed pathological angiogenesis in murine tumor and oxygen-induced retinopathy models. These results demonstrate that AMIGO2 is an important regulator of the PDK1–Akt pathway in ECs and suggest that interference of the PDK1–AMIGO2 interaction might be a novel pharmaceutical target for designing an Akt pathway inhibitor.  相似文献   
88.
Strongyloides stercoralis can cause systemic infection, termed strongyloidiasis, and gastrointestinal ulcer disease in immunocompromised patients. However, to our knowledge, there are no reported cases of comorbid gastric adenocarcinoma and S. stercoralis infection. Here, we report a case of an 81-year-old Korean man who presented with S. stercoralis infection coexisting with early gastric adenocarcinoma (T1aN0M0). S. stercoralis eggs, rhabditiform larvae, and adult females were observed in normal gastric and duodenal crypts. They were also observed in atypical glands representative of adenocarcinoma and adenoma. Preliminary laboratory tests revealed mild neutrophilic and eosinophilic leukocytosis. A routine stool test failed to detect rhabditiform larvae in the patient’s fecal sample; however, S. stercoralis was identified by PCR amplification and 18S rRNA sequencing using genomic DNA extracted from formalin-fixed paraffin-embedded tissues. Postoperatively, the patient had a persistent fever and was treated with albendazole for 7 days, which alleviated the fever. The patient was followed-up by monitoring and laboratory testing for 4 months postoperatively, and no abnormalities were observed thus far. The fact that S. stercoralis infection may be fatal in immunocompromised patients should be kept in mind when assessing high-risk patients.  相似文献   
89.
90.
Nanoporous network polymer nanocomposites with tunable pore size for size‐dependent selective ion transport are successfully prepared via the surface‐induced cross‐linking polymerization of methyl methacrylate (MMA) and 1,6‐hexanediol diacrylate (HDDA) on the surfaces of nanocrystalline TiO2 particles. The morphologies of the porous network polymer layer and nanopores were investigated by transmission electron microscopy (TEM), field emission scanning electron microscopy (FE‐SEM), and Brunauer–Emmett–Teller (BET) experiments. The porous layer size‐selectively screened the ions that contacted the nanocrystalline TiO2 particles, as demonstrated by ion conductivity measurements, electrochemical impedance spectroscopy (EIS), and transient absorption spectroscopy (TAS).  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