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991.
Xing Zhu Dhiraj Mannar Shanti S. Srivastava Alison M. Berezuk Jean-Philippe Demers James W. Saville Karoline Leopold Wei Li Dimiter S. Dimitrov Katharine S. Tuttle Steven Zhou Sagar Chittori Sriram Subramaniam 《PLoS biology》2021,19(4)
The recently reported “UK variant” (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments. 相似文献
992.
Omar Falou Ali Sadeghi-Naini Sameera Prematilake Ervis Sofroni Naum Papanicolau Sara Iradji Zahra Jahedmotlagh Sharon Lemon-Wong Jean-Philippe Pignol Eileen Rakovitch Judit Zubovits Jacqueline Spayne Rebecca Dent Maureen Trudeau Jean Francois Boileau Frances C Wright Martin J Yaffe Gregory J Czarnota 《Translational oncology》2013,6(1):17-24
PURPOSE: Ultrasound elastography is a new imaging technique that can be used to assess tissue stiffness. The aim of this study was to investigate the potential of ultrasound elastography for monitoring treatment response of locally advanced breast cancer patients undergoing neoadjuvant therapy. METHODS: Fifteen women receiving neoadjuvant chemotherapy had the affected breast scanned before, 1, 4, and 8 weeks following therapy initiation, and then before surgery. Changes in elastographic parameters related to tissue biomechanical properties were then determined and compared to clinical and pathologic tumor response after mastectomy. RESULTS: Patients who responded to therapy demonstrated a significant decrease (P < .05) in strain ratios and strain differences 4 weeks after treatment initiation compared to non-responding patients. Mean strain ratio and mean strain difference for responders was 81 ± 3% and 1 ± 17% for static regions of interest (ROIs) and 81 ± 3% and 6 ± 18% for dynamic ROIs, respectively. In contrast, these parameters were 102±2%, 110±17%, 101±4%, and 109±30% for non-responding patients, respectively. Strain ratio using static ROIs was found to be the best predictor of treatment response, with 100% sensitivity and 100% specificity obtained 4 weeks after starting treatment. CONCLUSIONS: These results suggest that ultrasound elastography can be potentially used as an early predictor of tumor therapy response in breast cancer patients. 相似文献
993.
994.
The conjugated nitro group has been included in the π system calculation within the MM2 force field. New parameters have been estimated by a statistical process from X-ray molecular structures recorded in the C.S.D.S. Comparison of the corresponding results with those given by the MM2(91) force field parameters show a clear improvement for dihedral and bond angles. For N-O and C-N bond lengths a slight global improvement is also observed. A closer examination of the results for the latter bond shows that sometimes MM2(91) gives better results for six membered ring nitro compounds. By contrast the parameters proposed here are more adapted to five membered ring derivatives. The derived linear relations permit the study of molecules over a wider range of π indices. The introduction of a correction factor to the calculated molecular π dipole moment in conjunction with a necessary reestimation of some σ-bond dipole moments also leads to improved total molecular dipole moments. 相似文献
995.
Jean-Philippe Draye Guy Cheron Gaëtan Libert Emile Godaux 《Biological cybernetics》1997,76(5):365-374
The neural integrator of the oculomotor system is a privileged field for artificial neural network simulation. In this paper,
we were interested in an improvement of the biologically plausible features of the Arnold-Robinson network. This improvement
was done by fixing the sign of the connection weights in the network (in order to respect the biological Dale's Law). We also
introduced a notion of distance in the network in the form of transmission delays between its units. These modifications necessitated
the introduction of a general supervisor in order to train the network to act as a leaky integrator. When examining the lateral
connection weights of the hidden layer, the distribution of the weights values was found to exhibit a conspicuous structure:
the high-value weights were grouped in what we call clusters. Other zones are quite flat and characterized by low-value weights. Clusters are defined as particular groups of adjoining
neurons which have strong and privileged connections with another neighborhood of neurons. The clusters of the trained network
are reminiscent of the small clusters or patches that have been found experimentally in the nucleus prepositus hypoglossi,
where the neural integrator is located. A study was conducted to determine the conditions of emergence of these clusters in
our network: they include the fixation of the weight sign, the introduction of a distance, and a convergence of the information
from the hidden layer to the motoneurons. We conclude that this spontaneous emergence of clusters in artificial neural networks,
performing a temporal integration, is due to computational constraints, with a restricted space of solutions. Thus, information
processing could induce the emergence of iterated patterns in biological neural networks.
Received: 18 September 1996 / Accepted in revised form: 7 January 1997 相似文献
996.
Gérard Lefranc Marie-Paule Lefranc Jeanine Seger Jean-Philippe Salier Leila Chakhachiro Jacques Loiselet 《Human genetics》1981,58(3):294-297
Summary Hypohaptoglobinaemia and ahaptoglobinaemia occurred in three generations, mainly to male members of a family. Also small amounts of haptolobin were detected in most of the female relatives. Haemolytic anaemia seemed unlikely and the glucose 6 phosphate dehydrogenase (G.6.P.D.) activity was normal. The probable genotype of these apparently healthy individuals was Hp
2/Hp
2. These preliminary data might suggest a defect in control of gene expression by steroid hormones. 相似文献
997.