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   42546篇
  免费   2766篇
  国内免费   17篇
  45329篇
  2023年   259篇
  2022年   581篇
  2021年   1048篇
  2020年   626篇
  2019年   792篇
  2018年   1096篇
  2017年   921篇
  2016年   1491篇
  2015年   2260篇
  2014年   2377篇
  2013年   3222篇
  2012年   3692篇
  2011年   3530篇
  2010年   2145篇
  2009年   1832篇
  2008年   2597篇
  2007年   2534篇
  2006年   2246篇
  2005年   2012篇
  2004年   1877篇
  2003年   1792篇
  2002年   1615篇
  2001年   387篇
  2000年   275篇
  1999年   353篇
  1998年   401篇
  1997年   274篇
  1996年   265篇
  1995年   247篇
  1994年   232篇
  1993年   231篇
  1992年   155篇
  1991年   167篇
  1990年   159篇
  1989年   125篇
  1988年   119篇
  1987年   108篇
  1986年   81篇
  1985年   116篇
  1984年   108篇
  1983年   79篇
  1982年   89篇
  1981年   84篇
  1980年   83篇
  1979年   80篇
  1978年   42篇
  1977年   57篇
  1976年   41篇
  1975年   46篇
  1973年   44篇
排序方式: 共有10000条查询结果,搜索用时 13 毫秒
101.
102.
Several approaches have been proposed to assess impacts on natural assemblages. Ideally, the potentially impacted site and multiple reference sites are sampled through time, before and after the impact. Often, however, the lack of information regarding the potential overall impact, the lack of knowledge about the environment in many regions worldwide, budgets constraints and the increasing dimensions of human activities compromise the reliability of the impact assessment. We evaluated the impact, if any, and its extent of a nuclear power plant effluent on sessile epibiota assemblages using a suitable and feasible sampling design with no ‘before’ data and budget and logistic constraints. Assemblages were sampled at multiple times and at increasing distances from the point of the discharge of the effluent. There was a clear and localized effect of the power plant effluent (up to 100 m from the point of the discharge). However, depending on the time of the year, the impact reaches up to 600 m. We found a significantly lower richness of taxa in the Effluent site when compared to other sites. Furthermore, at all times, the variability of assemblages near the discharge was also smaller than in other sites. Although the sampling design used here (in particular the number of replicates) did not allow an unambiguously evaluation of the full extent of the impact in relation to its intensity and temporal variability, the multiple temporal and spatial scales used allowed the detection of some differences in the intensity of the impact, depending on the time of sampling. Our findings greatly contribute to increase the knowledge on the effects of multiple stressors caused by the effluent of a power plant and also have important implications for management strategies and conservation ecology, in general.  相似文献   
103.
The cardiovascular benefits associated with diets rich in fruit and vegetables are thought to be due to phytochemicals contained in fresh plant material. However, whether processed plant foods provide the same benefits as unprocessed ones is an open question. Melanoidins from heat-processed apricots were isolated and their presence confirmed by colorimetric analysis and browning index. Oxidative injury of endothelial cells (ECs) is the key step for the onset and progression of cardiovascular diseases (CVD), therefore the potential protective effect of apricot melanoidins on hydrogen peroxide-induced oxidative mitochondrial damage and cell death was explored in human ECs. The redox state of cytoplasmic and mitochondrial compartments was detected by using the redox-sensitive, fluorescent protein (roGFP), while the mitochondrial membrane potential (MMP) was assessed with the fluorescent dye, JC-1. ECs exposure to hydrogen peroxide, dose-dependently induced mitochondrial and cytoplasmic oxidation. Additionally detected hydrogen peroxide-induced phenomena were MMP dissipation and ECs death. Pretreatment of ECs with apricot melanoidins, significantly counteracted and ultimately abolished hydrogen peroxide-induced intracellular oxidation, mitochondrial depolarization and cell death. In this regard, our current results clearly indicate that melanoidins derived from heat-processed apricots, protect human ECs against oxidative stress.  相似文献   
104.
105.
An early event in lung oncogenesis is loss of the tumour suppressor gene LIMD1 (LIM domains containing 1); this encodes a scaffold protein, which suppresses tumorigenesis via a number of different mechanisms. Approximately 45% of non-small cell lung cancers (NSCLC) are deficient in LIMD1, yet this subtype of NSCLC has been overlooked in preclinical and clinical investigations. Defining therapeutic targets in these LIMD1 loss-of-function patients is difficult due to a lack of ‘druggable’ targets, thus alternative approaches are required. To this end, we performed the first drug repurposing screen to identify compounds that confer synthetic lethality with LIMD1 loss in NSCLC cells. PF-477736 was shown to selectively target LIMD1-deficient cells in vitro through inhibition of multiple kinases, inducing cell death via apoptosis. Furthermore, PF-477736 was effective in treating LIMD1−/− tumours in subcutaneous xenograft models, with no significant effect in LIMD1+/+ cells. We have identified a novel drug tool with significant preclinical characterisation that serves as an excellent candidate to explore and define LIMD1-deficient cancers as a new therapeutic subgroup of critical unmet need.Subject terms: Targeted therapies, Non-small-cell lung cancer  相似文献   
106.
Analysis of microarrays performed in p53-, TAp63α- and ΔNp63α-inducible SaOs-2 cell lines allowed the identification of NCF2 mRNA upregulation in response to p53 induction. NCF2 gene encodes for p67phox, the cytosolic subunit of the NADPH oxidase enzyme complex. The recruitment of p67phox to the cell membrane causes the activation of the NADPH oxidase complex followed by the generation of NADP+ and superoxide from molecular oxygen. The presence of three putative p53 binding sites on the NCF2 promoter was predicted, and the subsequent luciferase and chromatin immunoprecipitation assays showed the activation of NCF2 promoter by p53 and its direct binding in vivo to at least one of the sites, thus confirming the hypothesis. NCF2 upregulation was also confirmed by real-time PCR in several cell lines after p53 activation. NCF2 knockdown by siRNA results in a significant reduction of ROS production and stimulates cell death, suggesting a protective function of Nox2-generated ROS in cells against apoptosis. These results provide insight into the redox-sensitive signaling mechanism that mediates cell survival involving p53 and its novel target NCF2/p67phox.  相似文献   
107.
Dispersal ability and field progeny production of augmentative released biological control agents depend on ecological adaptations of the particular species or strains used. Four species of the egg parasitoid genus Trichogramma were compared aiming to select suitable candidates for control of lepidopteran olive pests. Three of them (T. bourarachae Pintureau and Babault, T. cordubensis Vargas and Cabello, T. euproctidis Girault) had been previously collected from olive groves, whereas the commercially available strain used (T. evanescens Westwood) was originally isolated from sugarcane fields. During five consecutive field releases in an olive orchard near Cairo, dispersal and/or progeny production of these species was monitored using sentinel eggs placed at different heights in the release tree canopies as well as in neighboring trees (“distance effect”). The cardinal direction of dispersal was random for T. euproctidis and T. evanescens. Significant higher parasitism occurred on sentinel eggs placed on the middle part of tree canopy and highest parasitism was observed in trees where wasps had been released. Field progeny production was highest for T. bourarachae, followed by T. euproctidis and T. cordubensis. T. evanescens propagated less under field conditions. Inter-tree dispersal of all species except T. bourarachae was limited and, for biological control, releasing material should therefore be distributed on each olive tree, preferably also at different levels of the canopy.  相似文献   
108.
Thymomas are rare neoplasms that have an indolent growth with a preferentially intra-thoracic dissemination pattern. Surgery is currently the standard treatment of thymomas; however radiotherapy is often used in an adjuvant setting due to a high sensitivity of these tumors to such treatment. Postoperative entire hemithoracic irradiation has been used in selected Masaoka stage IVa cases after complete surgical excision of metastatic lesions.In the present article, the authors report three cases of Masaoka stage IVa thymoma that underwent entire hemithorax irradiation after surgical excision of metastatic lesions. The first two patients presented as stage IVa thymomas. The third case consisted of a pleural recurrence of a thymoma.Hemithoracic irradiation with low doses has been used by different authors; the available data shows that it is a well-tolerated treatment that could potentially lead to better loco-regional control and increased overall survival.  相似文献   
109.
Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multi-generational breast cancer predisposition is unknown. In this study, we used whole-exome sequencing of thirty-three individuals from 15 breast cancer families to identify potential predisposing genes. Our analysis identified families with heterozygous, deleterious mutations in the DNA repair genes FANCC and BLM, which are responsible for the autosomal recessive disorders Fanconi Anemia and Bloom syndrome. In total, screening of all exons in these genes in 438 breast cancer families identified three with truncating mutations in FANCC and two with truncating mutations in BLM. Additional screening of FANCC mutation hotspot exons identified one pathogenic mutation among an additional 957 breast cancer families. Importantly, none of the deleterious mutations were identified among 464 healthy controls and are not reported in the 1,000 Genomes data. Given the rarity of Fanconi Anemia and Bloom syndrome disorders among Caucasian populations, the finding of multiple deleterious mutations in these critical DNA repair genes among high-risk breast cancer families is intriguing and suggestive of a predisposing role. Our data demonstrate the utility of intra-family exome-sequencing approaches to uncover cancer predisposition genes, but highlight the major challenge of definitively validating candidates where the incidence of sporadic disease is high, germline mutations are not fully penetrant, and individual predisposition genes may only account for a tiny proportion of breast cancer families.  相似文献   
110.
Several members of a new family of non-sugar-type α-glucosidase inhibitors, bearing a phthalimide moiety connected to a variously substituted phenoxy ring by an alkyl chain, were synthesized and their activities were investigated. The efficacy of the inhibition activity appeared to be governed by the chain length of the substrate. Substrates possessing 10 carbons afforded the highest levels of activity, which were one to two orders of magnitude more potent than the known inhibitor 1-deoxynojirimycin (dNM). Furthermore, structure–activity relationship studies indicated a critical role of electron-withdrawing substituents at the phenoxy group for the activity. Derivatives bearing a chlorine atom along with a strong electron-withdrawing group, such as a nitro group, were the most potent of the series.  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