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991.
Motiwala H Kandre S Birar V Kadam KS Rodge A Jadhav RD Mahesh Kumar Reddy M Brahma MK Deshmukh NJ Dixit A Doshi L Gupte A Gangopadhyay AK Vishwakarma RA Srinivasan S Sharma M Nemmani KV Sharma R 《Bioorganic & medicinal chemistry letters》2011,21(19):5812-5817
The diacylglycerol acyltransferase enzyme, DGAT1, presents itself as a potential target for obesity as this enzyme is dedicated to the final committed step in triglyceride biosynthesis. Biphenyl ureas, exemplified by compound 4, have been reported to be potent hDGAT1 inhibitors. We have synthesized and evaluated 2-pyridyl and 3-pyridyl containing biaryl ureas as hDGAT1 inhibitors. Our aim was to incorporate a heteroaryl scaffold within these molecules thereby improving the cLogP profile and making these compounds more drug-like. Compounds within this series exhibited potent hDGAT1 inhibition when evaluated using an in vitro enzymatic assay. Selected compounds were also subjected to an oral fat tolerance test in mice where the percent triglyceride reduction versus a vehicle control was evaluated. Of the studied heteroaryl analogs compound 44 exhibited an in vitro IC(50) of 17nM and a plasma triglyceride reduction of 79% along with a 12-fold improvement in solubility over the biphenyl urea compound 4. 相似文献
992.
Kraft P Evangelista C Dacke M Labhart T Srinivasan MV 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2011,366(1565):703-708
While it is generally accepted that honeybees (Apis mellifera) are capable of using the pattern of polarized light in the sky to navigate to a food source, there is little or no direct behavioural evidence that they actually do so. We have examined whether bees can be trained to find their way through a maze composed of four interconnected tunnels, by using directional information provided by polarized light illumination from the ceilings of the tunnels. The results show that bees can learn this task, thus demonstrating directly, and for the first time, that bees are indeed capable of using the polarized-light information in the sky as a compass to steer their way to a food source. 相似文献
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994.
Srinivasan MV 《Current opinion in neurobiology》2011,21(4):535-543
Flying insects display remarkable agility, despite their diminutive eyes and brains. This review describes our growing understanding of how these creatures use visual information to stabilize flight, avoid collisions with objects, regulate flight speed, detect and intercept other flying insects such as mates or prey, navigate to a distant food source, and orchestrate flawless landings. It also outlines the ways in which these insights are now being used to develop novel, biologically inspired strategies for the guidance of autonomous, airborne vehicles. 相似文献
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996.
M. V. Srinivasan 《Biological cybernetics》1994,71(5):401-415
A technique for measuring the motion of a rigid, textured plane in the frontoparallel plane is developed and tested on synthetic
and real image sequences. The parameters of motion – translation in two dimensions, and rotation about a previously unspecified
axis perpendicular to the plane – are computed by a single-stage, non-iterative process which interpolates the position of
the moving image with respect to a set of reference images. The method can be extended to measure additional parameters of
motion, such as expansion or shear. Advantages of the technique are that it does not require tracking of features, measurement
of local image velocities or computation of high-order spatial or temporal derivatives of the image. The technique is robust
to noise, and it offers a simple, novel way of tackling the ‘aperture’ problem. An application to the computation of robot
egomotion is also described.
Received: 3 September 1993/Accepted in revised form: 16 April 1994 相似文献
997.
Sundar Srinivasan Dewayne Threet Leah E. Worton Brandon J. Ausk Steven D. Bain Edith M. Gardiner Ronald Y. Kwon Ted S. Gross 《PloS one》2014,9(1)
Age-related decline in periosteal adaptation negatively impacts the ability to utilize exercise to enhance bone mass and strength in the elderly. We recently observed that in senescent animals subject to cyclically applied loading, supplementation with Cyclosporin A (CsA) substantially enhanced the periosteal bone formation rates to levels observed in young animals. We therefore speculated that if the CsA supplement could enhance bone response to a variety of types of mechanical stimuli, this approach could readily provide the means to expand the range of mild stimuli that are robustly osteogenic at senescence. Here, we specifically hypothesized that a given CsA supplement would enhance bone formation induced in the senescent skeleton by both cyclic (1-Hz) and rest-inserted loading (wherein a 10-s unloaded rest interval is inserted between each load cycle). To examine this hypothesis, the right tibiae of senescent female C57BL/6 mice (22 Mo) were subjected to cyclic or rest-inserted loading supplemented with CsA at 3.0 mg/kg. As previously, we initially found that while the periosteal bone formation rate (p.BFR) induced by cyclic loading was enhanced when supplemented with 3.0 mg/kg CsA (by 140%), the response to rest-inserted loading was not augmented at this CsA dosage. In follow-up experiments, we observed that while a 30-fold lower CsA dosage (0.1 mg/kg) significantly enhanced p.BFR induced by rest-inserted loading (by 102%), it was ineffective as a supplement with cyclic loading. Additional experiments and statistical analysis confirmed that the dose-response relations were significantly different for cyclic versus rest-inserted loading, only because the two stimuli required distinct CsA dosages for efficacy. While not anticipated a priori, clarifying the complexity underlying the observed interaction between CsA dosage and loading type holds potential for insight into how bone response to a broad range of mechanical stimuli may be substantially enhanced in the senescent skeleton. 相似文献
998.
999.
When humans wish to move sideways, they almost never walk sideways, except for a step or two; they usually turn and walk facing forward. Here, we show that the experimental metabolic cost of walking sideways, per unit distance, is over three times that of forward walking. We explain this high metabolic cost with a simple mathematical model; sideways walking is expensive because it involves repeated starting and stopping. When walking sideways, our subjects preferred a low natural speed, averaging 0.575 m s−1 (0.123 s.d.). Even with no prior practice, this preferred sideways walking speed is close to the metabolically optimal speed, averaging 0.610 m s−1 (0.064 s.d.). Subjects were within 2.4% of their optimal metabolic cost per distance. Thus, we argue that sideways walking is avoided because it is expensive and slow, and it is slow because the optimal speed is low, not because humans cannot move sideways fast. 相似文献
1000.