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   1863篇
  免费   158篇
  国内免费   95篇
  2116篇
  2024年   9篇
  2023年   32篇
  2022年   47篇
  2021年   62篇
  2020年   65篇
  2019年   73篇
  2018年   92篇
  2017年   63篇
  2016年   57篇
  2015年   53篇
  2014年   105篇
  2013年   147篇
  2012年   87篇
  2011年   90篇
  2010年   68篇
  2009年   70篇
  2008年   74篇
  2007年   99篇
  2006年   92篇
  2005年   67篇
  2004年   67篇
  2003年   64篇
  2002年   47篇
  2001年   36篇
  2000年   43篇
  1999年   32篇
  1998年   37篇
  1997年   42篇
  1996年   31篇
  1995年   31篇
  1994年   22篇
  1993年   28篇
  1992年   30篇
  1991年   21篇
  1990年   13篇
  1989年   14篇
  1988年   12篇
  1987年   10篇
  1986年   7篇
  1985年   11篇
  1984年   15篇
  1983年   5篇
  1982年   9篇
  1981年   8篇
  1980年   7篇
  1979年   3篇
  1978年   5篇
  1977年   6篇
  1976年   3篇
  1974年   3篇
排序方式: 共有2116条查询结果,搜索用时 15 毫秒
131.
On 20 December 2017, a mature Triaenodon obesus was observed at Hanga Roa Bay, Rapa Nui (Easter Island) at c.18 m depth. This observation increases both the range of T. obesus in the Pacific Ocean and the number of elasmobranch species at Rapa Nui. In combination with other recent sightings further extending the southern range of this species during the Austral summer, sea surface temperature is suggested as key to southern dispersal.  相似文献   
132.
High density lipoprotein (HDL) has attracted the attention of biomedical community due to its well-documented role in atheroprotection. HDL has also been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral insulin sensitivity. Indeed, data from numerous studies strongly indicate that the functions of pancreatic β-cells, skeletal muscles and adipose tissue could benefit from improved HDL functionality. To better understand how changes in HDL structure may affect diet-induced obesity and type 2 diabetes we aimed at investigating the impact of Apoa1 or Lcat deficiency, two key proteins of peripheral HDL metabolic pathway, on these pathological conditions in mouse models. We report that universal deletion of apoa1 or lcat expression in mice fed western-type diet results in increased sensitivity to body-weight gain compared to control C57BL/6 group. These changes in mouse genome correlate with discrete effects on white adipose tissue (WAT) metabolic activation and plasma glucose homeostasis. Apoa1-deficiency results in reduced WAT mitochondrial non-shivering thermogenesis. Lcat-deficiency causes a concerted reduction in both WAT oxidative phosphorylation and non-shivering thermogenesis, rendering lcat?/? mice the most sensitive to weight gain out of the three strains tested, followed by apoa1?/? mice. Nevertheless, only apoa1?/? mice show disturbed plasma glucose homeostasis due to dysfunctional glucose-stimulated insulin secretion in pancreatic β-islets and insulin resistant skeletal muscles. Our analyses show that both apoa1?/? and lcat?/? mice fed high-fat diet have no measurable Apoa1 levels in their plasma, suggesting no direct involvement of Apoa1 in the observed phenotypic differences among groups.  相似文献   
133.
Insulin resistance (IR) is a villain role to the pathology of fatty liver diseases implicated in adipose tissue dysfunction, which is characterized by lipid droplets (LDs) accumulation and hypoxia-inducible factor 1α (HIF1α) related macrophage infiltration. HIF1α is required for its lipogenic actions in adipocytes, while and it regulates M1 and M2 polarization features of macrophages. Losartan has been shown to be an insulin sensitizer in obese states, actions involving in HIF1α signaling. However, the exact mechanisms accounting for these effects have not been fully elucidated. Therefore, GTT, ITT, and HOMA-IR were identified losartan alleviated IR signaling in obese mice. This alleviation may through inhibits HIF1α by suppressing STAT3-NF-κB signaling, which, in turn, revealed HIF1α-dependent decreases the angiogenesis pathway in adipose tissue, including regulation of VEGF and TGFβR2 levels. In white adipose tissue, a set of lipogenesis-related genes, Srebp1, Fas, and Scd-1 were markedly downregulated after losartan intervention, as well as reduced LDs size and LD-associated proteins, perilipin family proteins (PLINs) compared with obese mice. Losartan abolished macrophage infiltration with upregulation of M2 and inhibition of M1 macrophage markers in obese mice. Our data suggest that losartan attenuated obese-induced fatty liver, linked to alleviating inflammation in adipose tissues and a shift in M1/M2 macrophage balance. Furthermore, losartan might improve mitochondria biogenesis by upregulating SIRT1, PGC1α, UCP1, and mRNA of Tfam, Cd137, Tmem26, Ucp1 expression in white adipose tissue compared with the obese group. Taken together, losartan may improve IR and adipose dysfunction by inhibiting lipotoxicity and HIF1α pathways.  相似文献   
134.
The role of inflammatory mediators in dental pulp is unique. The local environment of pulp responds to any changes in the physiology that are highly fundamental, like odontoblast cell differentiation and other secretory activity. The aim of this review is to assess the role of cathelicidins based on their capacity to heal wounds, their immunomodulatory potential, and their ability to stimulate cytokine production and stimulate immune-inflammatory response in pulp and periapex. Accessible electronic databases were searched to find studies reporting the role of cathelicidins in pulpal inflammation and regeneration published between September 2010 and September 2020. The search was performed using the following databases: Medline, Scopus, Web of Science, SciELO and PubMed. The electronic search was performed using the combination of keywords “cathelicidins” and “dental pulp inflammation”. On the basis of previous studies, it can be inferred that LL-37 plays an important role in odontoblastic cell differentiation and stimulation of antimicrobial peptides. Furthermore, based on these outcomes, it can be concluded that LL-37 plays an important role in reparative dentin formation and provides signaling for defense by activating the innate immune system.  相似文献   
135.
为探明新疆野杏(Armeniaca vulgaris)种子萌发与幼苗生长对果肉和埋土深度的响应,以期为新疆野杏的天然更新与实生苗培育提供理论参考。通过2种果皮结构(有果肉和无果肉)的种子在不同埋土深度(地表至18.0 cm的14个梯度)对新疆野杏种子萌发和幼苗生长进行研究,旨在揭示果皮结构和埋土深度对新疆野杏种子萌发与成苗能力的影响。结果表明:果肉和埋土深度显著影响野杏种子的萌发、幼苗生长与质量(P<0.05)。埋土深度<3.0 cm不利于成苗,埋土深度>6.0 cm时,萌发能力与幼苗生长量随埋土深度的增加而降低,3.0~6.0cm为适宜埋土深度。无果肉种子萌发优于有果肉种子,萌发率、萌发指数、成苗率、活力指数分别增长了37.18%、3.88%、37.18%、26.59%,幼苗高、基径、叶片数量、根冠比、幼苗质量指数分别增长了36.99%、7.48%、68.69%、20.61%、14.29%,其萌发能力与幼苗生长量显著高于有果肉种子(P<0.05)。有无果肉种子的萌发和幼苗生长指标与埋土深度呈显著负相关(P<0.05)。研究结果表明,无果肉处理对新疆野杏种...  相似文献   
136.
徐圣东  周金洋  王丽  朱孟娟 《菌物学报》2021,40(6):1525-1537
利用漆酶(laccase)处理染料废水是近年来研究的热点.本研究以猴头菌Hericium erinaceus和金针菇Flammulina filiformis的发酵液为试验材料,通过硫酸铵沉淀、离子交换层析和超滤等方法,对发酵液中的漆酶进行了初步的分离纯化,然后分别研究了两种初提纯漆酶及其与小分子介体组成的漆酶介体系统...  相似文献   
137.
Selected strains of three species of white rot fungi, Pleurotus ostreatus, Phanerochaete chrysosporium and Trametes versicolor, were grown in sterilized soil from straw inocula. The respective colonization rates and mycelium density values decreased in the above mentioned order. Three- and four-ringed PAHs at 50 ppm inhibited growth of fungi in soil to some extent. The activities of fungal MnP and laccase (units per g dry weight of straw or soil), extracted with 50 mM succinate-lactate buffer (pH 4.5), were 5 to 20-fold higher in straw compared to soil. The enzyme activities per g dry soil in P. ostreatus and T. versicolor were similar, in contrast to P. chrysosporium, where they were extremely low. Compared to the aerated controls, P. ostreatus strains reduced the levels of anthracene, pyrene and phenanthrene by 81–87%, 84–93% and 41–64% within 2 months, respectively. During degradation of anthracene, all P. ostreatus strains accumulated anthraquinone. PAH removal rates in P. chrysosporium and T. versicolor soil cultures were much lower.  相似文献   
138.
Hormonal imprinting takes place perinatally at the first encounter between the developing receptor and its target hormone, resulting in the accomplishment of normal receptor development. In the presence of an excess of target hormone or the absence of it, or an excess of related molecules which can be bound by the receptor, faulty imprinting develops with life-long consequences. In previous experiments neonatal endorphin exposure caused a decrease in endorphin and serotonin content of peritoneal mast cells of adult animals. In the present experiment 25-day-old (weaned) female rats received 2 microg endorphin, and the endorphin as well as serotonin content of adult mast cells and white blood cells was studied by flow cytometry and confocal microscopy. Peritoneal lymphocytes and blood monocytes contained significantly (p<0.01) less endorphin and peritoneal mast cells less serotonin (p<0.07, i.e. of questionable significance) than the untreated control. The results bring attention to the possibility of durable imprinting of differentiating cells later in life and to the durable (possibly life-long) effect of an endorphin excess (perhaps caused by injury) manifested in the change of endorphin and serotonin content of immune cells.  相似文献   
139.
We investigated the molecular mechanism of the glucose effect on the regulation of chondrogenesis. Exposure of chick wing bud mesenchymal cells to high concentrations of glucose stimulated chondrogenesis 2–fold to 2.5-fold without affecting cell proliferation. Glucose increased protein levels and the membrane translocation of protein kinase C alpha (PKC), leading to a reduction of extracellular signal-regulated kinase (ERK) phosphorylation. Phosphorylation of p38 was also increased in a PKC-independent manner by glucose treatment. Glucose also increased cell adhesion molecules such as fibronectin, integrin 1, and N-cadherin at early stages and then decreased these adhesion molecules at later stages of chondrogenesis. These alterations in protein level of adhesion molecules and in the phosphorylation of mitogen-activated protein kinases by glucose were blocked by inhibition of PKC or p38 but were synergistically increased by the inhibition of ERK. Therefore, high doses of glucose induce the down-regulation of ERK activity via PKC and the up-regulation of p38 and result in the stimulation of chondrogenesis of chick mesenchymal cells through modulating the expression of adhesion molecules.This work was supported by the Korea Research Foundation (KRF-2000-DP0352)  相似文献   
140.
The quality of molecular dynamics (MD) simulations of proteins depends critically on the biomolecular force field that is used. Such force fields are defined by force-field parameter sets, which are generally determined and improved through calibration of properties of small molecules against experimental or theoretical data. By application to large molecules such as proteins, a new force-field parameter set can be validated. We report two 3.5 ns molecular dynamics simulations of hen egg white lysozyme in water applying the widely used GROMOS force-field parameter set 43A1 and a new set 45A3. The two MD ensembles are evaluated against NMR spectroscopic data NOE atom–atom distance bounds, 3JNH and 3J coupling constants, and 15N relaxation data. It is shown that the two sets reproduce structural properties about equally well. The 45A3 ensemble fulfills the atom–atom distance bounds derived from NMR spectroscopy slightly less well than the 43A1 ensemble, with most of the NOE distance violations in both ensembles involving residues located in loops or flexible regions of the protein. Convergence patterns are very similar in both simulations atom-positional root-mean-square differences (RMSD) with respect to the X-ray and NMR model structures and NOE inter-proton distances converge within 1.0–1.5 ns while backbone 3JHN-coupling constants and 1H– 15N order parameters take slightly longer, 1.0–2.0 ns. As expected, side-chain 3J-coupling constants and 1H– 15N order parameters do not reach full convergence for all residues in the time period simulated. This is particularly noticeable for side chains which display rare structural transitions. When comparing each simulation trajectory with an older and a newer set of experimental NOE data on lysozyme, it is found that the newer, larger, set of experimental data agrees as well with each of the simulations. In other words, the experimental data converged towards the theoretical result.  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