全文获取类型
收费全文 | 3267篇 |
免费 | 268篇 |
国内免费 | 2篇 |
专业分类
3537篇 |
出版年
2023年 | 8篇 |
2022年 | 44篇 |
2021年 | 57篇 |
2020年 | 46篇 |
2019年 | 55篇 |
2018年 | 75篇 |
2017年 | 63篇 |
2016年 | 97篇 |
2015年 | 157篇 |
2014年 | 176篇 |
2013年 | 191篇 |
2012年 | 279篇 |
2011年 | 239篇 |
2010年 | 176篇 |
2009年 | 147篇 |
2008年 | 207篇 |
2007年 | 236篇 |
2006年 | 201篇 |
2005年 | 179篇 |
2004年 | 202篇 |
2003年 | 150篇 |
2002年 | 137篇 |
2001年 | 29篇 |
2000年 | 22篇 |
1999年 | 19篇 |
1998年 | 34篇 |
1997年 | 21篇 |
1996年 | 22篇 |
1995年 | 20篇 |
1994年 | 20篇 |
1993年 | 14篇 |
1992年 | 11篇 |
1991年 | 11篇 |
1990年 | 8篇 |
1989年 | 15篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 10篇 |
1981年 | 9篇 |
1980年 | 11篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 8篇 |
1974年 | 6篇 |
1966年 | 5篇 |
1931年 | 6篇 |
排序方式: 共有3537条查询结果,搜索用时 15 毫秒
991.
Cortical circuits have been proposed to encode information by forming stable spatially structured attractors. Experimentally
in the primary somatosensory cortex of the monkey, temporally invariant stimuli lead to spatially structured activity patterns.
The purpose of this work is to study a recurrent cortical neural network model with lateral inhibition and examine what effect
additive random noise has on the networks' ability to form stable spatially structured representations of the stimulus pattern.
We show numerically that this network performs edge enhancement and forms statistically stationary, spatially structured responses
when the lateral inhibition is of moderate strength. We then derive analytical conditions on the connectivity matrix that
ensure stochasticly stable encoding of the stimulus spatial structure by the network. For stimuli whose strength falls in
the near linear region of the sigmoid, we are able to give explicit conditions on the eigenvalues of the connection matrix.
Finally, we prove that a network with a connection matrix, where the total excitation and inhibition impinging upon a neural
unit are nearly balanced, will yield stable spatial attractor responses.
Received: 16 October 1998 / Accepted in revised form: 25 November 1999 相似文献
992.
Trutko SM Akimenko VK Suzina NE Anisimova LA Shlyapnikov MG Baskunov BP Duda VI Boronin AM 《Archives of microbiology》2000,173(3):178-186
The terminal oxidases of the respiratory chain of seven strains of gram-negative bacteria were shown to be involved in the reduction of tellurite. The rate of tellurite reduction correlated with the intensity of respiration. The inhibitors of terminal oxidases, carbon monoxide and cyanide, inhibited the reduction of tellurite. In Pseudomonas aeruginosa PAO ML4262 and P. aeruginosa PAO ML4262 (pBS 10), the respiratory chain was found to contain three types of cytochrome c, one of which (the carbon monoxide-binding cytochrome c) was involved in the reduction of tellurite. Agrobacterium tumefaciens VKM B-1219, P. aeruginosa IBPM B-13, and Escherichia coli G0-102bd++ cells contained oxidases aa3, bb3, and bd, respectively. The respiratory chain of other strains contained two oxidases: E. coli DH5alpha of bb3- and bd-type, and Erwinia carotovora VKM B-567 of bo3- and bd-type. All the strains under study reduced tellurite with the formation of tellurium crystallites. Depending on the position of the active center of terminal oxidases in the plasma membrane, the crystallites appeared either in the periplasmic space [P. aeruginosa PAO ML4262 and P. aeruginosa PAO ML4262 (pBS10)], or on the outer surface of the membrane (A. tumefaciens VKM B-1219 and P. aeruginosa IBPM B-13), its inner surface (E. coli G0-102bd++), or on both surfaces (E. coli DHaalpha and E. carotovora VKM B-567). 相似文献
993.
François B Russell RJ Murray JB Aboul-ela F Masquida B Vicens Q Westhof E 《Nucleic acids research》2005,33(17):5677-5690
The crystal structures of six complexes between aminoglycoside antibiotics (neamine, gentamicin C1A, kanamycin A, ribostamycin, lividomycin A and neomycin B) and oligonucleotides containing the decoding A site of bacterial ribosomes are reported at resolutions between 2.2 and 3.0 Å. Although the number of contacts between the RNA and the aminoglycosides varies between 20 and 31, up to eight direct hydrogen bonds between rings I and II of the neamine moiety are conserved in the observed complexes. The puckered sugar ring I is inserted into the A site helix by stacking against G1491 and forms a pseudo base pair with two H-bonds to the Watson–Crick sites of the universally conserved A1408. This central interaction helps to maintain A1492 and A1493 in a bulged-out conformation. All these structures of the minimal A site RNA complexed to various aminoglycosides display crystal packings with intermolecular contacts between the bulging A1492 and A1493 and the shallow/minor groove of Watson–Crick pairs in a neighbouring helix. In one crystal, one empty A site is observed. In two crystals, two aminoglycosides are bound to the same A site with one bound specifically and the other bound in various ways in the deep/major groove at the edge of the A sites. 相似文献
994.
Ludwig M Doroszewicz J Seyberth HW Bökenkamp A Balluch B Nuutinen M Utsch B Waldegger S 《Human genetics》2005,117(2-3):228-237
ClC-5 is a member of the ClC family of voltage-gated chloride channels. Loss-of-function mutations of its corresponding gene (CLCN5) cause Dents disease, an X-linked kidney disorder, characterized by low-molecular weight proteinuria, hypercalciuria, nephrocalcinosis/nephrolithiasis, and progressive renal failure. Here, we examined the effect of different mutations on function and cellular trafficking of the recombinant protein. Mutant CLCN5 cDNAs were generated by site directed mutagenesis for two premature stop codon variants (R347X and M517IfsX528), and several missense mutations (C221R, L324R, G462 V, and R516 W). We also tested L521R (instead of L521RfsX526 observed) and mutants G506E and R648X (previously reported by others). After heterologous expression in Xenopus oocytes, ClC-5 channel activity and surface expression were determined by two-electrode voltage-clamp analysis and ClC-5 surface ELISA, respectively. Except for the R516 W and R648X variants, none of the mutated proteins induced functional chloride currents or reached the plasma membrane. This is readily understandable for the truncation mutations. Yet, the tested missense mutations are distributed over different transmembrane regions, implying that correct channel structure and orientation in the membrane is not only a prerequisite for proper ClC-5 function but also for Golgi exit. Interestingly, the R648X mutant although functionally compromised, displayed a significant increase in surface expression. This finding might be explained by the deletion of a ClC-5 carboxy-terminal PY-like internalization signal, which in turn impairs channel removal from the membrane. Our observations further imply that recruitment of ClC-5 to alternative routes (plasma membrane or early endosomes) in the trans-Golgi network is mediated via different signal sequences.Electronic Supplementary Material Supplementary material is available for this article at . 相似文献
995.
Pulse EPR, 55Mn-ENDOR and ELDOR-detected NMR experiments were performed on the S2-state of the oxygen-evolving complex from spinach Photosystem II. The novel technique of random acquisition in ENDOR was used to suppress heating artefacts. Our data unambiguously shows that four Mn ions have significant hyperfine coupling constants. Numerical simulation of the 55Mn-ENDOR spectrum allowed the determination of the principal values of the hyperfine interaction tensors for all four Mn ions of the oxygen-evolving complex. The results of our 55Mn-ENDOR experiments are in good agreement with previously published data [Peloquin JM et al. (2000) J Am Chem Soc 122: 10926–10942]. For the first time ELDOR-detected NMR was applied to the S2-state and revealed a broad peak that can be simulated numerically with the same parameters that were used for the simulation of the 55Mn-ENDOR spectrum. This provides strong independent support for the assigned hyperfine parameters. 相似文献
996.
Estephan R Englander J Arshava B Samples KL Becker JM Naider F 《Biochemistry》2005,44(35):11795-11810
The yeast Saccharomyces cerevisiae alpha-factor pheromone receptor (Ste2p) was used as a model G protein-coupled receptor (GPCR). A 73-mer multidomain fragment of Ste2p (residues 267-339) containing the third extracellular loop, the seventh transmembrane domain, and 40 residues of the cytosolic tail (E3-M7-24-T40) was biosynthesized fused to a carrier protein. The multidomain fusion protein (designated M7FP) was purified to near homogeneity as judged by HPLC and characterized by mass spectrometry. In minimal medium, 30-40 mg of M7FP were obtained per liter of culture. The 73-residue peptide was released from its carrier by CNBr and obtained in wild-type, (15)N, and (13)C/(15)N forms. The E3-M7-24-T40 peptide integrated into 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-rac-(1-glycerol)] and dodecylphosphocholine micelles at concentrations (200-500 microM) suitable for NMR investigations. HSQC experiments performed in organic solvents and detergent micelles on (15)N-labeled E3-M7-24-T40 showed a clear dispersion of the nitrogen-amide proton correlation cross-peaks indicative of a pure, uniformly labeled molecule that assumed a partially ordered structure. NOE connectivities, chemical shift indices, J-coupling analysis, and structural modeling suggested that in trifluoroethanol/water (1:1) helical subdomains existed in both the transmembrane and cytoslic tail of the multidomain peptide. Similar conclusions were reached in chloroform/methanol/water (4:4:1). As the cytosolic tail participates in down-regulation of Ste2p, the helical regions in the Ste2p tail may play a role in protein-protein interactions involved in endocytosis. 相似文献
997.
BACKGROUND: Helicobacter pylori is a curved microaerophilic Gram-negative bacterium considered as a risk factor for gastric cancer. The aim of this study was to find an association between burning sensations, acid taste, halitosis, and lingual hyperplasia with the effect of H. pylori on the mouth. MATERIALS AND METHODS: A total of 124 subjects with different gastric diseases were studied: 46 patients with burning, halitosis and lingual dorsum hyperplasia and 78 patients with other diseases. RESULTS: The detection of H. pylori in the oral cavity by histopathologic diagnosis and molecular biology was confirmed in 40/46 (87%) patients with burning, halitosis, and lingual hyperplasia, and in 2/78 (2.6%) subjects with other diseases. Chi2: 91.26 (p < .001) Mantel-Haenszel. CONCLUSION: This trial showed an association between H. pylori and burning, halitosis, and lingual hyperplasia, and further considered this bacterium a risk factor for gastric infection. 相似文献
998.
Penberthy JK Cox D Breton M Robeva R Kalbfleisch ML Loboschefski T Kovatchev B 《Applied psychophysiology and biofeedback》2005,30(1):31-51
When analyzed separately, data from small studies provide only limited information with limited clinical generalizability, due to small sample size, differing assessments, and limited scope. In this methodological paper we outline a theoretical framework for performing meta-analysis of data obtained from disparate studies using disparate tests, based on calibration of the data from such studies and tests into a unified probability scale. We apply this method to combine the data from five studies examining the diagnostic abilities of different assessments of Attention Deficit/Hyperactivity Disorder (ADHD), including behavioral rating scales and EEG assessments. The studies enrolled a total of 111 subjects, 56 ADHD and 55 controls. Each individual study had a small sample focused on a specific age/gender group, for example 8 boys ages 6–10, and generally had insufficient power to detect statistically significant differences. No gender, or age comparisons were possible within any single study. However, when calibrated and combined, the data resulted in a clear separation between ADHD versus non-ADHD groups in males below the age of 16 (p < 0.001), males above the age of 16, (p = 0.015), females below the age of 16, (p = 0.0014), and females above the age of 16, (p = 0.0022).We conclude that if data from various studies using various tests are made comparable, the resulting combined sample size and the increased diversity of the combined sample lead to increased significance of the statistical tests and allow for cross-sectional comparisons, which are not possible within each individual study. 相似文献
999.
Cathepsin S is unique among mammalian cysteine cathepsins in being active and stable at neutral pH. We show that autocatalytic activation of procathepsin S at low pH is a bimolecular process that is considerably accelerated (approximately 20-fold) by glycosaminoglycans and polysaccharides such as dextran sulfate, chondroitin sulfates A and E, and dermatan sulfate through electrostatic interaction with the proenzyme. Procathepsin S is also shown to undergo autoactivation at neutral pH in the presence of dextran sulfate with t1/2 of approximately 20 min at pH 7.5. This novel property of procathepsin S may have implications in pathological conditions associated with the appearance of active cathepsins outside lysosomes. 相似文献
1000.
A protein assay based on colloidal gold conjugates with trypsin 总被引:2,自引:0,他引:2
The standard sol particle immunoassay (SPIA) is based on a biospecific aggregation of gold nanoparticle conjugates, followed by conventional spectrophotometry. Here we propose a novel SPIA format that uses microtitration immunological plates and an enzyme-linked immunosorbent assay reader. The novel and standard assays are exemplified by determination of immunoglobulin G by using 15-nm colloidal gold-protein A conjugates. We also describe a novel sol particle-trypsin assay using conjugates of gold nanoparticles with trypsin. The method is based on measuring spectral extinction changes caused by the addition of protein to a conjugate solution. The changes in the extinction spectra are presumed to be related to aggregation of gold nanoparticles caused by polyvalent binding of protein molecules to the trypsin molecules of the conjugates. 相似文献