首页 | 官方网站   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   80973篇
  免费   4547篇
  国内免费   116篇
工业技术   85636篇
  2023年   640篇
  2022年   738篇
  2021年   2326篇
  2020年   1619篇
  2019年   1711篇
  2018年   2786篇
  2017年   2783篇
  2016年   2952篇
  2015年   2193篇
  2014年   2950篇
  2013年   5770篇
  2012年   4855篇
  2011年   5019篇
  2010年   3922篇
  2009年   3666篇
  2008年   3634篇
  2007年   3141篇
  2006年   2529篇
  2005年   2127篇
  2004年   1917篇
  2003年   1766篇
  2002年   1543篇
  2001年   1118篇
  2000年   1065篇
  1999年   1247篇
  1998年   5540篇
  1997年   3494篇
  1996年   2322篇
  1995年   1363篇
  1994年   1158篇
  1993年   1112篇
  1992年   403篇
  1991年   405篇
  1990年   350篇
  1989年   374篇
  1988年   350篇
  1987年   316篇
  1986年   293篇
  1985年   348篇
  1984年   291篇
  1983年   213篇
  1982年   243篇
  1981年   270篇
  1980年   253篇
  1979年   177篇
  1978年   170篇
  1977年   370篇
  1976年   723篇
  1975年   138篇
  1973年   142篇
排序方式: 共有10000条查询结果,搜索用时 62 毫秒
81.
82.
Microbiological contamination of chicken meat depends on the conditions under which the animals are reared, slaughtered and processed. The aim of this study was to determine the influence of farm origin and processing stages at slaughterhouse on the microbial safety and quality of chicken. Samples of chicken carcasses from three different farms were taken from a slaughterhouse. Mesophiles, Escherichia coli, coagulase positive Staphylococcci counts, presence of Listeria monocytogenes,Campylobacter and Salmonella were determined at five sampling points: after defeathering, after evisceration, after washing, after chilling and after cutting. Chilling reduced log numbers of mesophiles, coagulase positive Staphylococci and E. coli by 0.85, 1.52 and 2.2 log units, respectively. Salmonella was not detected after chilling. High prevalence of Campylobacter spp was observed at all the stages ranging between 84% and 100%. L. monocytogenes was not detected in chicken carcasses after defeathering. However, it was detected after evisceration and after washing and chilling. The most critical stage for Lmonocytogenes contamination was the portioning operation, the prevalence in breast and legs being 88% and 84%, respectively.  相似文献   
83.
Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.  相似文献   
84.
Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.  相似文献   
85.
The ‐centroid problem or leader–follower problem is generalized considering different customer choice rules where a customer may use facilities belonging to different firms, if the difference in travel distance (or time) is small enough. Assuming essential goods, some particular customer choice rules are analyzed. Linear programming formulations for the generalized ‐medianoid and ‐centroid problems are presented and an exact solution approach is applied. Some computational examples are included.  相似文献   
86.
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.  相似文献   
87.
d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant.  相似文献   
88.
Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions.  相似文献   
89.
Steryl glucosides (SG) are common contaminants in biodiesel that form precipitates, which form and cause problems due to fouling during transport and storage. Therefore, their quantification is necessary to assess the quality of this fuel. The methods currently available for SG analysis require expensive instrumentation, need a previous concentration step by solid‐phase extraction (SPE) or are of limited use for the quantitative assessment. We developed an enzymatic method for SG quantification in biodiesel samples based on the hydrolysis of the glucoside catalyzed by a broadly specific beta glucosidase and the subsequent determination of the glucose released by the reaction. The method is non‐expensive, sensitive and was adapted to 96‐well format fluorescence plate reader, making it useful for the parallel assay of multiple samples. The enzymatic assay presented here represent a valuable tool for both quality control and the development of improved biodiesel production and purification procedures.  相似文献   
90.
Metal Science and Heat Treatment - The effect of solid boronizing at 950°C for 2 and 4 h on the phase composition, microstructure, hardness and abrasive wear of steel AISI 304L is studied...  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-23

京公网安备 11010802026262号