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Qilu Ye Yedan Feng Yanxia Yin Frédérick Faucher Mark A. Currie Mona N. Rahman Jin Jin Shanze Li Qun Wei Zongchao Jia 《Cellular signalling》2013,25(12):2661-2667
Calcineurin is the only known calmodulin (CaM) activated protein phosphatase, which is involved in the regulation of numerous cellular and developmental processes and in calcium-dependent signal transduction. Although commonly assumed that CaM displaces the autoinhibitory domain (AID) blocking substrate access to its active site, the structural basis underlying activation remains elusive. We have created a fused ternary complex (CBA) by covalently linking three polypeptides: CaM, calcineurin regulatory B subunit (CnB) and calcineurin catalytic A subunit (CnA). CBA catalytic activity is comparable to that of fully activated native calcineurin in the presence of CaM. The crystal structure showed virtually no structural change in the active site and no evidence of CaM despite being covalently linked. The asymmetric unit contains four molecules; two parallel CBA pairs are packed in an antiparallel mode and the large cavities in crystal packing near the calcineurin active site would easily accommodate multiple positions of AID-bound CaM. Intriguingly, the conformation of the ordered segment of AID is not altered by CaM; thus, it is the disordered part of AID, which resumes a regular α-helical conformation upon binding to CaM, which is displaced by CaM for activation. We propose that the structural basis of calcineurin activation by CaM is through displacement of the disordered fragment of AID which otherwise impedes active site access. 相似文献
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Mariana G. Figueiro Andrew Bierman John D. Bullough Mark S. Rea 《Chronobiology international》2013,30(4):726-739
Light treatment has been used as a non-pharmacological tool to help mitigate poor sleep quality frequently found in older people. In order to increase compliance to non-pharmacological light treatments, new, more efficacious light-delivery systems need to be developed. A prototype personal light-treatment device equipped with low brightness blue light-emitting diodes (LEDs) (peak wavelength near 470 nm) was tested for its effectiveness in suppressing nocturnal melatonin, a measure of circadian stimulation. Two levels of corneal irradiance were set to deliver two prescribed doses of circadian light exposure. Eleven older subjects, between 51 and 80 yrs of age who met the selection criteria, were exposed to a high and a low level of light for 90 min on separate nights from the personal light-treatment device. Blood and saliva samples were collected at prescribed times for subsequent melatonin assay. After 1 h of light exposure, the light-induced nocturnal melatonin suppression level was about 35% for the low-light level and about 60% for the high-light level. The higher level of blue light suppressed melatonin more quickly, to a greater extent over the course of the 90 min exposure period, and maintained suppression after 60 min. The constant exposure of the low-light level resulted in a decrease in nocturnal melatonin suppression for the last sampling time, whereas for the high-light level, suppression continued throughout the entire exposure period. The present study performed with healthy adults suggests that the tested personal light-treatment device might be a practical, comfortable, and effective way to deliver light treatment to those suffering from circadian sleep disorders; however, the acceptance and effectiveness of personal light-treatment devices by older people and by other segments of the population suffering from sleep disorders in a real-life situation need to be directly tested. (Author correspondence: figuem@rpi.edu) 相似文献
956.
Mark R. Wilson Marc W. Allard Eric W. Brown 《Cladistics : the international journal of the Willi Hennig Society》2013,29(4):449-461
The forensic evaluation of bacterial pathogens presents new challenges to the forensic science community. This review examines bacterial pathogens as objects of forensic comparison, focusing on their nucleic acid sequences as an important aspect of the comparison process. Because of the clonal propagation of most bacterial pathogens, a phylogenetic approach to understanding the diversity and using this understanding to address common forensic questions is explored. As a general phylogenetic framework is now employed in human mitochondrial DNA analysis, we will use the relevant concepts and approaches common in this area to develop this approach further. We also address the impact of the current ease and prevalence of whole‐genome DNA sequence analysis in the forensic comparison process. 相似文献
957.
In situ hybridization for trk A mRNA in trigeminal ganglion neurons retrogradely labeled with FluoroGold from the mandibular incisor demonstrated limited expression of the high-affinity nerve growth factor (NGF) receptor in this presumptive nociceptor population. Immunocytochemistry using polyclonal anti- trk A antibodies confirmed this result and extended it to show low levels of trk A protein expression in afferents labeled from the cornea. Less than 10% of the cells innervating the incisor, and ~15% of those innervating the cornea, were trk A-positive in adult and neonatal mice. This proportion is considerably lower than that observed in Dorsal Root Ganglion nociceptors, in which ~80% in neonates and ~40% in adults express trk A (Molliver and Snider, J Comp Neurol 381: 428-438, 1997). Presumptive trigeminal nociceptors were further identified on the basis of expression of Calcitonin gene related peptide. In the entire ganglion, ~43% of the trk A-positive cells were CGRP-positive, and ~44% of the CGRP-positive cells were trk A-positive. Most trk A-positive cells that were CGRP-negative were medium-to-large diameter, while most of those that were CGRP-positive but trk A-negative were small diameter. Only ~5% of trk A-positive cells labeled from the incisor, and ~10% from the cornea, were CGRP-positive. Approximately 15% of the corneal or pulpal afferent neurons expressed ret -immunoreactivity. These results suggest that trigeminal nociceptors differ from spinal nociceptors in several significant ways. Differences in neurotrophic requirements may be related to differences in target tissues, in embryonic origin of some trigeminal ganglion cells, or in the timing of down-regulation of trk A expression in trigeminal ganglion cells. 相似文献
958.
The Pacinian channel has been implicated in the perception of fine textures (Hollins et al. , Somatosens Mot Res 18: 253-262, 2001a). In the present study, we investigate candidate codes for Pacinian-mediated roughness perception. We use a Hall effect transducer to record the vibrations elicited in the skin when a set of textured surfaces is passively presented to the index finger. The peak frequency of the vibrations is found to decrease systematically as spatial period increases. The power of the vibrations--weighted according to the spectral sensitivity of the Pacinian system--increases with spatial period for all but the coarsest surfaces. By varying the scanning velocity, we manipulate the temporal and intensive characteristics of the texture-induced vibrations and assess the effect of the manipulation on perceived roughness. We find that doubling the scanning velocity does not result in the substantial decrease in roughness predicted by a frequency theory of vibrotactile roughness perception. On the other hand, the effects of speed on roughness match those of speed on power. We propose that the roughness of a fine surface (spatial period<200 7 m) is a function of the Pacinian-weighted power of the vibrations it elicits. 相似文献
959.
Global warming and excess nitrogen deposition can exert strong impacts on aquatic populations, communities, and ecosystems. However, experimental data to establish clear cause-and-effect relationships in naturally complex field conditions are scarce in aquatic environments. Here, we describe the design and performance of a unique outdoor enclosure facility used to simulate warming, increased nitrogen supply, and both factors combined in a littoral freshwater wetland dominated by common reed, Phragmites australis. The experimental system effectively simulated a 2.8 °C climate warming scenario over an extended period, capturing the natural temperature variations in the wetland at diel and seasonal scales with only small deviations. Excess nitrogen supply enhanced nitrate concentrations especially in winter when it was associated with increased concentration of ammonium and dissolved organic carbon. Nitrogen also reduced dissolved oxygen concentrations, particularly in the summer. Importantly, by stimulating biological activity, warming enhanced the nitrogen uptake capacity of the wetland during the winter, emphasizing the need for multifactorial global change experiments that examine both warming and nitrogen loading in concert. Establishing similar experiments across broad environmental gradients holds great potential to provide robust assessments of the impacts of climate change on shallow aquatic ecosystems. 相似文献
960.
Yui Osanai Damian S. Bougoure Helen L. Hayden Mark J. Hovenden 《Plant and Soil》2013,368(1-2):419-431