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991.
Pipecolic Acid Hydroxylases: A Monophyletic Clade among cis‐Selective Bacterial Proline Hydroxylases that Discriminates l‐Proline
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Johanna Mattay Dr. Wolfgang Hüttel 《Chembiochem : a European journal of chemical biology》2017,18(15):1523-1528
Proline hydroxylases are iron(II)/2‐oxoglutarate‐dependent enzymes that hydroxylate l ‐proline and derivatives, such as l pipecolic acid, which is the six‐membered‐ring homologue of l ‐proline. It has been established that there is a distinct group of conserved bacterial enzymes that hydroxylate l ‐pipecolic acid and trans‐3‐ and trans‐4‐methyl‐l ‐proline, but virtually no l ‐proline. This allows the organism to produce hydroxyproline congeners without hydroxylation of the physiologically omnipresent l ‐proline. In vitro conversions showed that the substrate spectrum of the pipecolic acid hydroxylases GetF (from a Streptomyces sp.; producer of the tetrapeptide antibiotic GE81112) and PiFa (from Frankia alni) overlaps that of proline hydroxylases, except for the nonacceptance of l ‐proline and smaller homologues. Distinct and conserved residues were determined for both types of enzymes. However, site‐directed mutagenesis in GetF did not yield variants that accepted l ‐proline; this suggested a complex interaction of several residues around the active site, which resulted in delicate changes in substrate specificity. This is supported by substrate docking in a homology model of GetF, which revealed an altered orientation for l ‐proline relative to that of preferred substrates. 相似文献
992.
Dual,Site‐Specific Modification of Antibodies by Using Solid‐Phase Immobilized Microbial Transglutaminase
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Dr. Philipp R. Spycher Christian A. Amann Jöri E. Wehrmüller David R. Hurwitz Olivier Kreis Daniel Messmer Andreas Ritler Dr. Andreas Küchler Alain Blanc Dr. Martin Béhé Prof. Dr. Peter Walde Prof. Dr. Roger Schibli 《Chembiochem : a European journal of chemical biology》2017,18(19):1923-1927
Microbial transglutaminase (MTG) was stably solid‐phase immobilized on glass microbeads by using a second‐generation dendronized polymer. Immobilized MTG enabled the efficient generation of site‐specifically conjugated proteins, including antibody fragments, as well as whole antibodies through distinct glutamines and, unprecedentedly, also through lysines with various bifunctional substrates with defined stoichiometries. With this method, we generated dual, site‐specifically modified antibodies comprising a fluorescent probe and a metal chelator for radiolabeling—a strategy anticipated to design antibodies for imaging and simultaneous therapy. Furthermore, we provide evidence that immobilized MTG features higher siteselectivity than soluble MTG. 相似文献
993.
Xiaoyu Zhang Dr. Shiqiang Zhang Prof. Seung Joon Baek Prof. Michael D. Best 《Chembiochem : a European journal of chemical biology》2017,18(16):1578-1582
Cell surface glycoproteins are commonly aberrant in disease and act as biomarkers that facilitate diagnostics. Mucin‐1 (MUC1) is a prominent example, exhibiting truncated glycosylation in cancer. We present herein a boronic acid microplate assay for sensitive and high‐throughput detection of such glycoproteins. The immobilization of biotin–boronic acid 1 onto streptavidin plates generated a multivalent surface for glycoprotein recruitment and detection. We first validated the binding properties of 1 in solution through titrations with alizarin dye. Next, the microplate assay was explored through horseradish peroxidase (HRP) analysis as a proof‐of‐concept glycoprotein with chemiluminescence detection. Finally, this platform was applied for the detection of MUC1 directly from MCF‐7 human breast cancer cell lysates by using an HRP‐tagged antibody that targets the cancerous form of this glycoprotein. Sensitive, dose‐dependent detection of MUC1 was observed, showcasing the efficacy of this platform for detecting disease‐associated glycoproteins. 相似文献
994.
Inside Back Cover: Ancestral Haloalkane Dehalogenases Show Robustness and Unique Substrate Specificity (ChemBioChem 14/2017)
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995.
Dr K. Berndt 《Measurement》1987,5(4):159-166
Correlation analysis has become an important research tool in the investigation of signals and systems behaviour. We report on a special opto-electronic cross-correlator in which a silicon avalanche photodiode is used as the main component. The internal gain of this photodiode is pulse-modulated with 330 ps FWHM at 126 MHz repetition rate, or is modulated sinusoidally at frequencies of up to 882 MHz, respectively. In the pulsed mode, very weak repetitive optical pulses can be detected with 3 × 10−3 photons per pulse sensitivity, and with 10 ps timing accuracy. The second mode offers time-selective signal rejection capabilities with 3 ps time resolution. The opto-electronic cross-correlator can be used in displacement and distance measurement, robotics, time dispersion analysis in optical fibres, transient absorption spectroscopy, fluorescence decay measurement, lifetime-selective fluorescence detection, and in fluorescence signal suppression in Raman spectroscopy. 相似文献
996.
Dr Amy J. C. Trappey C. Richard Liu 《The International Journal of Advanced Manufacturing Technology》1993,8(5):297-304
The geometric and topological specification of a workpiece boundary is usually represented in a specific data format in a CAD database. To retrieve a set of workpiece data, to analyse its shape in addition to the machining requirements, and to determine the proper fixture configuration accordingly, are not trivial tasks when a part has a complicated shape. The real challenge is to recognise and synthesise the shape of a workpiece from its data representation. Consequently, the decision for fixturing can be made when the shape of a workpiece and the relationship of the shape and the fixturing configuration can be derived by a systematic methodology. In this paper, a projective spatial occupancy enumeration (PSOE) approach is applied as a representational and manipulating scheme for developing algorithms in automatic fixture configuration. The workpiece is projected onto the working plane of the fixture baseplate. A 2D projection is defined as a matrix of cells which can represent a workpiece with an arbitrary shape. Using a discrete search based upon the matrix of cells, the fixture types and their locations are generated according to a set of heuristic algorithms. This work is a generalisation and extension of previous works for prismatic parts. The same methodology is equally applicable in general robot grasping. 相似文献
997.
Dr. Jessica S. Kelsey Dr. Tamas Geczy Nancy E. Lewin Dr. Noemi Kedei Colin S. Hill Julia S. Selezneva Christopher J. Valle Wonhee Woo Dr. Inna Gorshkova Dr. Peter M. Blumberg 《Chembiochem : a European journal of chemical biology》2014,15(8):1131-1144
The C1 domain, which represents the recognition motif on protein kinase C for the lipophilic second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters, has emerged as a promising therapeutic target for cancer and other indications. Potential target selectivity is markedly enhanced both because binding reflects ternary complex formation between the ligand, C1 domain, and phospholipid, and because binding drives membrane insertion of the C1 domain, permitting aspects of the C1 domain surface outside the binding site, per se, to influence binding energetics. Here, focusing on charged residues identified in atypical C1 domains which contribute to their loss of ligand binding activity, we showed that increasing charge along the rim of the binding cleft of the protein kinase C δ C1 b domain raises the requirement for anionic phospholipids. Correspondingly, it shifts the selectivity of C1 domain translocation to the plasma membrane, which is more negatively charged than internal membranes. This change in localization is most pronounced in the case of more hydrophilic ligands, which provide weaker membrane stabilization than do the more hydrophobic ligands and thus contributes an element to the structure–activity relations for C1 domain ligands. Coexpressing pairs of C1‐containing constructs with differing charges each expressing a distinct fluorescent tag provided a powerful tool to demonstrate the effect of increasing charge in the C1 domain. 相似文献
998.
Prof. Dr. Zhiqing Zhang Dr. Mark A. Eckert Dr. M. Monsur Ali Linan Liu Dr. Dong‐Ku Kang Elizabeth Chang Dr. Egest J. Pone Prof. Dr. Leonard S. Sender Prof. Dr. David A. Fruman Prof. Dr. Weian Zhao 《Chembiochem : a European journal of chemical biology》2014,15(9):1268-1273
We report a simple, versatile, multivalent ligand system that is capable of specifically and efficiently modulating cell‐surface receptor clustering and function. The multivalent ligand is made of a polymeric DNA scaffold decorated with biorecognition ligands (i.e., antibodies) to interrogate and modulate cell receptor signaling and function. Using CD20 clustering‐mediated apoptosis in B‐cell cancer cells as a model system, we demonstrated that our multivalent ligand is significantly more effective at inducing apoptosis of target cancer cells than its monovalent counterpart. This multivalent DNA material approach represents a new chemical biology tool to interrogate cell receptor signaling and functions and to potentially manipulate such functions for the development of therapeutics. 相似文献
999.
Synthesis of Novel Phosphonic‐Type Activity‐Based Probes for Neutrophil Serine Proteases and Their Application in Spleen Lysates of Different Organisms
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Dr. Renata Grzywa Dr. Ewa Burchacka Maria Łęcka Dr. Łukasz Winiarski Maciej Walczak Agnieszka Łupicka‐Słowik Dr. Magdalena Wysocka Prof. Timo Burster Dr. Kamila Bobrek Dr. Keri Csencsits‐Smith Prof. Adam Lesner Dr. Marcin Sieńczyk 《Chembiochem : a European journal of chemical biology》2014,15(17):2605-2612
Neutrophils are a type of granulocyte important in the “first line of defense” of the innate immune system. Upon activation, they facilitate the destruction of invading microorganisms by the production of superoxide radicals, as well as the release of the enzymatic contents of their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, as well as the recently discovered neutrophil serine protease 4 (NSP4). Under normal conditions, the proteolytic activity of neutrophil proteases is tightly regulated by endogenous serpins; however, this mechanism can be subverted during tissue stress, thereby resulting in the uncontrolled activity of serine proteases, which induce chronic inflammation and subsequent pathology. Herein, we describe the development of low‐molecular‐weight activity‐based probes that specifically target the active sites of neutrophil proteases. 相似文献
1000.
Hui Zhi Shirley Lee Prof. Weng Kee Leong Dr. Siden Top Dr. Anne Vessières 《ChemMedChem》2014,9(7):1453-1457
A structure–activity relationship (SAR) study of the triosmium carbonyl cluster Os3(CO)10(NCCH3)2 was carried out with a series of clusters of the general formula Os3(CO)12?nLn, cationic osmium clusters and a hemi‐labile maltolato‐Os cluster. The SAR results showed that good solubility in DMSO and at least one vacant site are required for cytotoxicity. In vitro evaluation of these new compounds showed that some are selectively active against estrogen receptor (ER)‐independent MDA‐MB‐231 breast cancer cell lines relative to ER‐dependent MCF‐7 breast cancer cells, suggesting that the compounds have a different biological target specific to MDA‐MB‐231 cells. In particular, the maltolato cluster exhibits strong antiproliferative activity, with an IC50 value of 3 μM after only 24 h incubation. Additionally, biochemical assays conducted with the cationic cluster show that it induces apoptosis, although a biological target has not yet been identified. Further research to establish the molecular targets of these compounds and to develop improved organometallic clusters as potential breast cancer therapeutics is underway. 相似文献