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991.
Deniz Caylioglu Rieke Johanna Meyer Dana Hellmold Carolin Kubelt Michael Synowitz Janka Held-Feindt 《International journal of molecular sciences》2021,22(7)
Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences. 相似文献
992.
993.
Michael A. Clegg Prof. Nicholas C. O. Tomkinson Dr. Rab K. Prinjha Dr. Philip G. Humphreys 《ChemMedChem》2019,14(4):362-385
The bromodomain and extra terminal (BET) family of bromodomain-containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high-quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non-BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non-BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non-BET bromodomains as tractable therapeutic targets. 相似文献
994.
Andreas Zehnsdorf Norman Stock Juliane Richter Michael Blumberg Roland A. Müller 《化学,工程师,技术》2016,88(8):1138-1144
There is increasing interest worldwide in the decentralized treatment of gray water. Since ground‐level areas are generally costly, gray‐water treatment can also be carried out using helophyte mats on the roofs of buildings as an alternative. Alongside the water treatment itself, this process also has a positive effect on the indoor climate in the building. In a test carried out under realistic conditions, it was shown that a helophyte mat with a root‐layer depth of 0.1 m and with hydraulic loads per unit up to 15 L m?2d?1 is suitable for treating typical gray water from a residential building. 相似文献
995.
The interest in black raspberry products has been increasing due to its flavor and potential health benefits. While black raspberries grown in North America are Rubus occidentalis, there has been some confusion regarding the identity of black raspberry grown in Korea (known as bokbunja; Rubus coreanus). As such, there is a need to define the anthocyanin profile of R. coreanus fruit collected from a verified source. We analyzed three genotypes of bokbunja fruit for anthocyanin profiles. While each varied in its anthocyanin proportions and total concentration, bokbunja fruit contained three anthocyanins: cyanidin-3-glucoside, cyanidin-3-rutinoside, and pelargonidin-3-glucoside, and lacked the xylose containing glycosides characteristic of R. occidentalis: cyanidin-3-sambubioside, and cyanidin-3-xylosylrutinoside. Due to mix-ups of bokbunja identity, research claiming to be conducted on bokbunja fruit requires confirmation that the fruit was sourced from a correctly identified plant. The distinct anthocyanin profiles between the two species can be used to confirm plant identity. 相似文献
996.
Lucie Čechovská Karel Cejpek Michael Konečný Jan Velíšek 《European Food Research and Technology》2011,233(3):367-376
Despite available reports on phenolic composition and antioxidant capacity (AOC) of fresh plums and prunes, there is a scarcity
of published knowledge on the antioxidants formed and/or released during the drying process in the literature. To evaluate
the compounds participating in reducing capacity of prunes, we compared aqueous and methanol extracts of fresh plums, commercial
prunes and home-made prunes prepared at different drying temperatures using an HPLC method with amperometric detection (HPLC-ECD).
The prunes dried at high temperature (90 °C, 18 h) in kitchen or laboratory oven with restricted ventilation gave up to 3.3 times
higher electrochemical capacity (EC) than fresh plums (dry matter; P. domestica cv. Domestica) in dependence on production protocol. Drying at 60 °C (low-temperature drying) for 18 h did not change the
EC significantly. Yet, lower EC was found in commercial tenderized prunes with sorbate; they were by a factor of 1.1–8.2 lower
in EC than the prepared low-temperature prunes. The principle responsible for the increase in EC in the prunes prepared at
high temperatures is 2,3-dihydro-3,5-dihydroxy-6-methyl-(4H)-pyran-4-one (DDMP). It was not detected until 74 °C was set during isothermal 18 h drying or until 6 h of drying passed
at 90oC drying. The ultimate acceptable dwell-time for the preparation of conveniently eatable prunes dried at 90oC under
the conditions used was assessed to 12 h. The EC of plums and prunes as well as the role of DDMP was confirmed by the use
of several methods for the assessment of AOC-DPPH• assay, β-carotene bleaching method, Oxipres test and Schaal oven test. 相似文献
997.
Dragos Horvath Michael Lisurek Bernd Rupp Ronald Kühne Edgar Specker Jens von Kries Didier Rognan C. David Andersson Fredrik Almqvist Mikael Elofsson Per‐Anders Enqvist Anna‐Lena Gustavsson Nikita Remez Jordi Mestres Gilles Marcou Alexander Varnek Marcel Hibert Jordi Quintana Ronald Frank 《ChemMedChem》2014,9(10):2309-2326
This work describes a collaborative effort to define and apply a protocol for the rational selection of a general‐purpose screening library, to be used by the screening platforms affiliated with the EU‐OPENSCREEN initiative. It is designed as a standard source of compounds for primary screening against novel biological targets, at the request of research partners. Given the general nature of the potential applications of this compound collection, the focus of the selection strategy lies on ensuring chemical stability, absence of reactive compounds, screening‐compliant physicochemical properties, loose compliance to drug‐likeness criteria (as drug design is a major, but not exclusive application), and maximal diversity/coverage of chemical space, aimed at providing hits for a wide spectrum of drugable targets. Finally, practical availability/cost issues cannot be avoided. The main goal of this publication is to inform potential future users of this library about its conception, sources, and characteristics. The outline of the selection procedure, notably of the filtering rules designed by a large committee of European medicinal chemists and chemoinformaticians, may be of general methodological interest for the screening/medicinal chemistry community. The selection task of 200K molecules out of a pre‐filtered set of 1.4M candidates was shared by five independent European research groups, each picking a subset of 40K compounds according to their own in‐house methodology and expertise. An in‐depth analysis of chemical space coverage of the library serves not only to characterize the collection, but also to compare the various chemoinformatics‐driven selection procedures of maximal diversity sets. Compound selections contributed by various participating groups were mapped onto general‐purpose self‐organizing maps (SOMs) built on the basis of marketed drugs and bioactive reference molecules. In this way, the occupancy of chemical space by the EU‐OPENSCREEN library could be directly compared with distributions of known bioactives of various classes. This mapping highlights the relevance of the selection and shows how the consensus reached by merging the five different 40K selections contributes to achieve this relevance. The approach also allows one to readily identify subsets of target‐ or target‐class‐oriented compounds from the EU‐OPENSCREEN library to suit the needs of the diverse range of potential users. The final EU‐OPENSCREEN library, assembled by merging five independent selections of 40K compounds from various expert groups, represents an excellent example of a Europe‐wide collaborative effort toward the common objective of building best‐in‐class European open screening platforms. 相似文献
998.
Production of aromatics by catalytic fast pyrolysis of cellulose in a bubbling fluidized bed reactor 下载免费PDF全文
Pranav U. Karanjkar Robert J. Coolman George W. Huber Michael T. Blatnik Saba Almalkie Stephen M. de Bruyn Kops Triantafillos J. Mountziaris William C. Conner 《American Institute of Chemical Engineers》2014,60(4):1320-1335
Catalytic fast pyrolysis of cellulose was studied at 500°C using a ZSM‐5 catalyst in a bubbling fluidized bed reactor constructed from a 4.92‐cm ID pipe. Inert gas was fed from below through the distributor plate and from above through a vertical feed tube along with cellulose. Flowing 34% of the total fluidization gas through the feed tube led to the optimal mixing of the pyrolysis vapors into the catalyst bed, which experimentally corresponded to 29.5% carbon aromatic yield. Aromatic yield reached a maximum of 31.6% carbon with increasing gas residence time by changing the catalyst bed height. Increasing the hole‐spacing in the distributor plate was shown to have negligible effect on average bubble diameter and hence did not change the product distribution. Aromatic yields of up to 39.5% carbon were obtained when all studied parameters were optimized. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1320–1335, 2014 相似文献
999.
Jyothilakshmi Vadassery Michael Reichelt Guillermo H. Jimenez-Aleman Wilhelm Boland Axel Mithöfer 《Journal of chemical ecology》2014,40(7):676-686
The majority of plant defenses against insect herbivores are coordinated by jasmonate (jasmonic acid, JA; (+)-7-iso-jasmonoyl-L-isoleucine, JA-Ile)-dependent signaling cascades. Insect feeding and mimicking herbivory by application of oral secretions (OS) from the insect induced both cytosolic Ca2+ and jasmonate-phytohormone elevation in plants. Here it is shown that in Arabidopsis thaliana upon treatment with OS from lepidopteran Spodoptera littoralis larvae, the antibiotic neomycin selectively blocked the accumulation of OS-induced Ca2+ elevation and level of the bioactive JA-Ile, in contrast to JA level. Furthermore, neomycin treatment affected the downstream expression of JA-Ile-responsive genes, VSP2 and LOX2, in Arabidopsis. The neomycin-dependent reduced JA-Ile level is partially due to increased CYP94B3 expression and subsequent JA-Ile turn-over to12-hydroxy-JA-Ile. It is neither due to the inhibition of the enzymatic conjugation process nor to substrate availability. Thus, blocking Ca2+ elevation specifically controls JA-Ile accumulation and signaling, offering an insight into role of calcium in defense against insect herbivory. 相似文献
1000.
Carnivore Attractant or Plant Elicitor? Multifunctional Roles of Methyl Salicylate Lures in Tomato Defense 总被引:1,自引:0,他引:1
Elizabeth Rowen Michael Gutensohn Natalia Dudareva Ian Kaplan 《Journal of chemical ecology》2017,43(6):573-585
Synthetic plant volatile lures attract natural enemies, but may have non-target effects due to the multifunctional nature of volatile signals. For example, methyl salicylate (MeSA) is used to attract predators, yet also serves as a signaling hormone involved in plant pathogen defense. We investigated the consequences of deploying MeSA lures to attract predators for tomato (Solanum lycopersicum) defense against herbivores. To understand the spatial distribution of the lure’s effect, we exposed tomatoes in the field to MeSA along a linear distance gradient and induced defenses by simulating feeding by hornworm caterpillars in a fully crossed factorial design (+/? MeSA, +/? herbivory). Subsequently, we analyzed activity of several defensive proteins (protease inhibitors, polyphenol oxidase, peroxidase), development of hornworm larvae (Manduca sexta), growth of fungal pathogens (Cladosporium and Alternaria), and attractiveness to herbivores and predators. Overall, MeSA-exposed plants were more resistant to both insects and pathogens. Secondary pathogen infection was reduced by 25% in MeSA exposed plants, possibly due to elevated polyphenol oxidase activity. Interestingly, we found that lures affected plant pathogen defenses equivalently across all distances (up to 4 m away) indicating that horizontal diffusion of a synthetic volatile may be greater than previously assumed. While thrips avoided colonizing hornworm– damaged tomato plants, this induced resistance was not observed upon pre-exposure to MeSA, suggesting that MeSA suppresses the repellant effect induced by herbivory. Thus, using MeSA lures in biological control may inadvertently protect crops from pathogens, but has mixed effects on plant resistance to insect herbivores. 相似文献