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   1845篇
  免费   149篇
  2023年   19篇
  2022年   42篇
  2021年   63篇
  2020年   49篇
  2019年   57篇
  2018年   82篇
  2017年   77篇
  2016年   83篇
  2015年   120篇
  2014年   112篇
  2013年   141篇
  2012年   136篇
  2011年   144篇
  2010年   77篇
  2009年   67篇
  2008年   97篇
  2007年   76篇
  2006年   88篇
  2005年   55篇
  2004年   54篇
  2003年   47篇
  2002年   40篇
  2001年   34篇
  2000年   26篇
  1999年   18篇
  1998年   8篇
  1997年   18篇
  1996年   7篇
  1995年   6篇
  1994年   3篇
  1993年   5篇
  1992年   14篇
  1991年   15篇
  1990年   9篇
  1989年   7篇
  1988年   16篇
  1987年   13篇
  1986年   7篇
  1985年   4篇
  1984年   8篇
  1983年   4篇
  1982年   3篇
  1981年   4篇
  1979年   6篇
  1978年   4篇
  1977年   3篇
  1976年   3篇
  1973年   5篇
  1972年   4篇
  1970年   2篇
排序方式: 共有1994条查询结果,搜索用时 15 毫秒
131.
To investigate the alterations of glucose homeostasis and variables of the insulin‐like growth factor‐1 (IGF‐1) growth system in sedentary and trained diabetic (TD) rats, Wistar rats were divided into sedentary control (SC), trained control (TC), sedentary diabetic (SD), and TD groups. Diabetes was induced by Alloxan (35 mg kg?1 b.w.). Training program consisted of swimming 5 days week?1, 1 h day?1, during 8 weeks. Rats were sacrificed and blood was collected for determinations of serum glucose, insulin, growth hormone (GH), IGF‐1, and IGF binding protein‐3 (IGFBP‐3). Muscle and liver were removed to evaluate glycogen content. Cerebellum was extracted to determinate IGF‐1 content. Diabetes decreased serum GH, IGF‐1, IGFBP‐3, liver glycogen, and cerebellum IGF‐1 peptide content in baseline condition. Physical training recovered liver glycogen and increased serum and cerebellum IGF‐1 peptide in diabetic rats. Physical training induces important metabolic and hormonal alterations that are associated with an improvement in glucose homeostasis and serum and cerebellum IGF‐1 concentrations. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   
132.
The inflammatory cytokine interferon-gamma (IFNγ) is crucial for immunity against intracellular pathogens such as the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (CD). IFNγ is a pleiotropic cytokine which regulates activation of immune and non-immune cells; however, the effect of IFNγ in the central nervous system (CNS) and astrocytes during CD is unknown. Here we show that parasite persists in the CNS of C3H/He mice chronically infected with the Colombian T. cruzi strain despite the increased expression of IFNγ mRNA. Furthermore, most of the T. cruzi-bearing cells were astrocytes located near IFNγ+ cells. Surprisingly, in vitro experiments revealed that pretreatment with IFNγ promoted the infection of astrocytes by T. cruzi increasing uptake and proliferation of intracellular forms, despite inducing increased production of nitric oxide (NO). Importantly, the effect of IFNγ on T. cruzi uptake and growth is completely blocked by the anti-tumor necrosis factor (TNF) antibody Infliximab and partially blocked by the inhibitor of nitric oxide synthesis L-NAME. These data support that IFNγ fuels astrocyte infection by T. cruzi and critically implicate IFNγ-stimulated T. cruzi-infected astrocytes as sources of TNF and NO, which may contribute to parasite persistence and CNS pathology in CD.  相似文献   
133.
DNA replication in higher eukaryotes initiates at thousands of origins according to a spatio-temporal program. The ATR/Chk1 dependent replication checkpoint inhibits the activation of later firing origins. In the Xenopus in vitro system initiations are not sequence dependent and 2-5 origins are grouped in clusters that fire at different times despite a very short S phase. We have shown that the temporal program is stochastic at the level of single origins and replication clusters. It is unclear how the replication checkpoint inhibits late origins but permits origin activation in early clusters. Here, we analyze the role of Chk1 in the replication program in sperm nuclei replicating in Xenopus egg extracts by a combination of experimental and modelling approaches. After Chk1 inhibition or immunodepletion, we observed an increase of the replication extent and fork density in the presence or absence of external stress. However, overexpression of Chk1 in the absence of external replication stress inhibited DNA replication by decreasing fork densities due to lower Cdk2 kinase activity. Thus, Chk1 levels need to be tightly controlled in order to properly regulate the replication program even during normal S phase. DNA combing experiments showed that Chk1 inhibits origins outside, but not inside, already active clusters. Numerical simulations of initiation frequencies in the absence and presence of Chk1 activity are consistent with a global inhibition of origins by Chk1 at the level of clusters but need to be combined with a local repression of Chk1 action close to activated origins to fit our data.  相似文献   
134.
135.

Background

Microalgae are a potential source of sustainable commodities of fuels, chemicals and food and feed additives. The current high production costs, as a result of the low areal productivities, limit the application of microalgae in industry. A first step is determining how the different production system designs relate to each other under identical climate conditions. The productivity and photosynthetic efficiency of Nannochloropsis sp. CCAP 211/78 cultivated in four different outdoor continuously operated pilot-scale photobioreactors under the same climatological conditions were compared. The optimal dilution rate was determined for each photobioreactor by operation of the different photobioreactors at different dilution rates.

Results

In vertical photobioreactors, higher areal productivities and photosynthetic efficiencies, 19–24 g m?2 day?1 and 2.4–4.2 %, respectively, were found in comparison to the horizontal systems; 12–15 g m?2 day?1 and 1.5–1.8 %. The higher ground areal productivity in the vertical systems could be explained by light dilution in combination with a higher light capture. In the raceway pond low productivities were obtained, due to the long optical path in this system. Areal productivities in all systems increased with increasing photon flux densities up to a photon flux density of 30 mol m?2 day?1. Photosynthetic efficiencies remained constant in all systems with increasing photon flux densities. The highest photosynthetic efficiencies obtained were; 4.2 % for the vertical tubular photobioreactor, 3.8 % for the flat panel reactor, 1.8 % for the horizontal tubular reactor, and 1.5 % for the open raceway pond.

Conclusions

Vertical photobioreactors resulted in higher areal productivities than horizontal photobioreactors because of the lower incident photon flux densities on the reactor surface. The flat panel photobioreactor resulted, among the vertical photobioreactors studied, in the highest average photosynthetic efficiency, areal and volumetric productivities due to the short optical path. Photobioreactor light interception should be further optimized to maximize ground areal productivity and photosynthetic efficiency.
  相似文献   
136.
137.
BackgroundTreatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis.MethodologyWe used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay.ConclusionsFunctional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone.  相似文献   
138.
The nematode Caenorhabditis elegans is a central laboratory model system in almost all biological disciplines, yet its natural life history and population biology are largely unexplored. Such information is essential for in‐depth understanding of the nematode's biology because its natural ecology provides the context, in which its traits and the underlying molecular mechanisms evolved. We characterized natural phenotypic and genetic variation among North German C. elegans isolates. We used the unique opportunity to compare samples collected 10 years apart from the same compost heap and additionally included recent samples for this and a second site, collected across a 1.5‐year period. Our analysis revealed significant population genetic differentiation between locations, across the 10‐year time period, but for only one location a trend across the shorter time frame. Significant variation was similarly found for phenotypic traits of likely importance in nature, such as choice behavior and population growth in the presence of pathogens or naturally associated bacteria. Phenotypic variation was significantly influenced by C. elegans genotype, time of isolation, and sampling site. The here studied C. elegans isolates may provide a valuable, genetically variable resource for future dissection of naturally relevant gene functions.  相似文献   
139.
Tubastraea tagusensis, a coral native to the Galapagos Archipelago, has successfully established and invaded the Brazilian coast where it modifies native tropical rocky shore and coral reef communities. In order to understand the processes underlying the establishment of T. tagusensis, we tested whether Maxent, a tool for species distribution modeling, based on the native range of T. tagusensis correctly forecasted the invasion range of this species in Brazil. The Maxent algorithm was unable to predict the Brazilian coast as a suitable environment for the establishment of T. tagusensis. A comparison between these models and a principal component analysis (PCA) allowed us to examine the environmental dissimilarity between the two occupied regions (native and invaded) and to assess the species' occupied niche breadth. According to the PCA results, lower levels of chlorophyll‐a and nitrate on the Atlantic coast segregate the Brazilian and Galapagos environments, implying that T. tagusensis may have expanded its realized niche during the invasion process. We tested the possible realized niche expansion in T. tagusensis by assuming that Tubastraea spp. have similar fundamental niches, which was supported by exploring the environmental space of T. coccinea, a tropical‐cosmopolitan congener of T. tagusensis. We believe that the usage of Maxent should be treated with caution, especially when applied to biological invasion (or climate change) scenarios where the target species has a highly localized native (original) distribution, which may represent only a small portion of its fundamental niche, and therefore a violation of a SDM assumption.  相似文献   
140.
The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection.  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