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81.
Recent work has elucidated the potential of important new therapeutic paradigms, including metronomic delivery and chronotherapy, in which the precise timing and location of therapeutic administration has a significant impact on efficacy and toxicity. New drug delivery architectures are needed to not only release drug continuously at precise rates, but also synchronize their release with circadian cycles. We present an actively controlled nanofluidic membrane that exploits electrophoresis to control the magnitude, duration, and timing of drug release. The membrane, produced using high precision silicon fabrication techniques, has platinum electrodes integrated at the inlet and outlet that allow both amplification and reversal of analyte delivery with low applied voltage (at or below 2 VDC). Device operation was demonstrated with solutions of both fluorescein isothiocyanate conjugated bovine serum albumin and lysozyme using fluorescence spectroscopy, fluorescence microscopy, and a lysozyme specific bio-assay and has been characterized for long-term molecular release and release reversibility. Through a combination of theoretical and experimental analysis, the relative contributions of electrophoresis and electroosmosis have been investigated. The membrane's clinically relevant electrophoretic release rate at 2 VDC exceeds the passive release by nearly one order of magnitude, demonstrating the potential to realize the therapeutic paradigm goal. 相似文献
82.
The finite element absolute nodal coordinate formulation (ANCF) is often used in modeling very flexible bodies in multibody system (MBS) applications. This formulation leads to a constant mass matrix, allowing for an efficient sparse matrix implementation. Nonetheless, the use of the ANCF finite elements to model stiff structures can lead to high frequencies associated with ANCF coupled deformation modes, as discussed in the literature. Implicit numerical integration methods can be effectively used to develop efficient procedures for the solution of MBS differential/algebraic equations. Most existing implicit integration algorithms, however, require numerical differentiation of the equations of motion, and some of these integration methods do not ensure that the kinematic algebraic constraint equations are satisfied at all levels (position, velocity, and acceleration). Because of these limitations, existing implicit integration methods can be less accurate and less efficient when used to solve large scale MBS applications. In order to circumvent this problem, the two-loop implicit sparse matrix numerical integration (TLISMNI) method was proposed for the solution of MBS differential/algebraic equations. The TLISMNI method does not require numerical differentiation of the forces and allows for an efficient sparse matrix implementation. This paper discusses TLISMNI implementation issues including the step size selection, the error control, and the effect of the numerical damping. The relation between the step size selection and the structure stiffness is also discussed. The use of the computer implementation described in this paper is demonstrated by solving very stiff structure problems using the Hilber?CHughes?CTaylor (HHT) method, which includes numerical damping. An eigenvalue analysis and Fast Fourier Transform (FFT) are performed in order to identify the fundamental modes of deformation and demonstrate that the contributions of these fundamental modes can be erroneously damped out when some other implicit integration methods are used. The TLISMNI method, on the other hand, captures the contributions of these fundamental modes. The results, obtained using the TLISMNI method, are compared with the results obtained using other methods including the implicit HHT-I3 and the explicit Adams integration methods. The results obtained show that the TLISMNI method can be five times faster than the other two methods when no numerical damping is considered. 相似文献
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84.
Sylvester I. Omoruyi Abobaker S. Ibrakaw Okobi E. Ekpo James S. Boatwright Christopher N. Cupido Ahmed A. Hussein 《Molecules (Basel, Switzerland)》2021,26(13)
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP+ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP+-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses. 相似文献
85.
Basel F. Abu-Sharkh Adam M. Giri Ibnelwaleed A. Hussein 《European Polymer Journal》2004,40(6):1177-1182
Microstructure of linear low-density polyethylene (LLDPE) with linear high-density polyethylene (HDPE) is investigated by molecular dynamics (MD) simulation. The branch content of LLDPE was varied from 10 to 60 branches/1000 C. An equimolar mixture of each of the two polymers is simulated in the NVT ensemble at 500 K and at average experimental densities of the two polymer melts. Initially, chains of LLDPE and HDPE were completely mixed and evolution of conformations with time was monitored. The blends were found to microphase separate when the branch content of LLDPE exceeded 30 branches/1000 C. At 40 branches/1000 C, the two polymers displayed partial microphase separation and complete microphase separation was observed at 60 branches/1000 C. Substantial short-range order and mismatch of molecular conformations is observed in the microphase-separated systems. 相似文献
86.
Angular distributions of the48Ti(d, t)47Ti and47Ti(d, t)46Ti reactions have been measured atE d =19.5 MeV and analyzed by DWBA. The data suggest an explanation of the48Ti(d, t)47Ti ground state transition by means of a [f 7 2/5 ·f 5/2]0+ neutron component in the ground state of48Ti. 相似文献
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Facile syntheses of pyrazole, pyridine, pyrimidine and pyrazolo[3,4-d]pyrimidine derivatives have been achieved by the reaction of β-enamino nitrile 2a with hydrazines, phenyl isothiocyanate, thiourea and active methylene reagents. The β-enamino ketone 2e with the same reagents affords 3,5-dimethyl heterocyclic ring systems. 相似文献
90.