全文获取类型
收费全文 | 4299篇 |
免费 | 319篇 |
国内免费 | 2篇 |
专业分类
4620篇 |
出版年
2023年 | 12篇 |
2022年 | 35篇 |
2021年 | 58篇 |
2020年 | 47篇 |
2019年 | 51篇 |
2018年 | 53篇 |
2017年 | 74篇 |
2016年 | 96篇 |
2015年 | 190篇 |
2014年 | 191篇 |
2013年 | 268篇 |
2012年 | 342篇 |
2011年 | 364篇 |
2010年 | 230篇 |
2009年 | 209篇 |
2008年 | 310篇 |
2007年 | 251篇 |
2006年 | 259篇 |
2005年 | 239篇 |
2004年 | 228篇 |
2003年 | 246篇 |
2002年 | 210篇 |
2001年 | 58篇 |
2000年 | 47篇 |
1999年 | 58篇 |
1998年 | 55篇 |
1997年 | 42篇 |
1996年 | 48篇 |
1995年 | 46篇 |
1994年 | 32篇 |
1993年 | 21篇 |
1992年 | 38篇 |
1991年 | 15篇 |
1990年 | 28篇 |
1989年 | 18篇 |
1988年 | 19篇 |
1987年 | 16篇 |
1986年 | 12篇 |
1985年 | 16篇 |
1984年 | 14篇 |
1983年 | 17篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1971年 | 4篇 |
排序方式: 共有4620条查询结果,搜索用时 15 毫秒
1.
Identifying common prognostic factors in genomic cancer studies: A novel index for censored outcomes
Background
With the growing number of public repositories for high-throughput genomic data, it is of great interest to combine the results produced by independent research groups. Such a combination allows the identification of common genomic factors across multiple cancer types and provides new insights into the disease process. In the framework of the proportional hazards model, classical procedures, which consist of ranking genes according to the estimated hazard ratio or the p-value obtained from a test statistic of no association between survival and gene expression level, are not suitable for gene selection across multiple genomic datasets with different sample sizes. We propose a novel index for identifying genes with a common effect across heterogeneous genomic studies designed to remain stable whatever the sample size and which has a straightforward interpretation in terms of the percentage of separability between patients according to their survival times and gene expression measurements. 相似文献2.
Use of ATP bioluminescence measurements for the estimation of biomass during biological humification
Summary The development of the microflora during the humification of grape pulp has been investigated by the determination of ATP using the bioluminescence technique. Several extraction methods were tested including the use of dimethylsulphoxide, trichloroacetic acid, grinding and ultrasonification. Dimethylsulphoxide and ultrasonification for 15 sec appeared to be the most effective. The ATP extract was stabilized when it was mixed with 0.75 mM glycine, 4.4 mM Mg-EDTA, pH 7.5 and frozen. The relative error of the ATP assay by bioluminescence did not exceed 6.5%. This method allowed us to show that at least five distinct reproducible microbial phases exist during grape pulp humification. These results show that the microbial biomass changes noticeably and at distinct times during composting. 相似文献
3.
Expression of alternatively spliced mRNA variants at specific stages of development or in specific cells and tissues contributes to the functional diversity of the human genome. Aberrations in alternative splicing were found as a cause or a contributing factor to the development, progression, or maintenance of numerous diseases. The use of antisense oligonucleotides (ON) to modify aberrant expression patterns of alternatively spliced mRNAs is a novel means of potentially controlling such diseases. Oligonucleotides can be designed to repair genetic mutations, to modify genomic sequences in order to compensate for gene deletions, or to modify RNA processing in order to improve the effects of the underlying gene mutation. Steric block ON approach have proven to be effective in experimental model for various diseases. Here, we describe our experience in investigating two strategies for ON delivery: ON conjugation with basic peptides and lipid-based particulate system (lipoplex). Basic peptides or Cell Penetrating Peptides (CPP) such as the TAT-derived peptide appear to circumvent many problems associated with ON and drug delivery. This strategy may represent the next paradigm in our ability to modulate cell function and offers a unique avenue for the treatment of disease. Lipoplexes result from the intimate interaction of ON with cationic lipids leading to ON carrying particles able to be taken up by cells and to release ON in the cytoplasm. We have used as an experimental model the correction of a splicing alteration of the mutated β-globin intron causing thalassemia. Data on cell penetration and efficacy of correction of specific steric block ON delivered either by basic peptides or lipoplex are described. A comparison of the properties of both delivery systems is made respective to the use of this new class of therapeutic molecules. 相似文献
4.
We report the case of a 59-year-old woman, investigated for disabling pain of the left thigh, unrelated to any traumatic event. Interrogation had found diffuse pain of myalgia-type and arthralgia-type for approximately a year without local inflammatory signs and insufficiency fractures of both calcaneus two years before. The Technetium 99m-labeled hydroxymethylene diphosphonate (99mTc-HDP) whole-body bone scintigraphy evidenced multiple hot spots on the higher third of left femur, rib cage, sternum, scapulae, pelvis, right hip and both calcaneus. Moreover, a more diffuse and heterogeneous prominent uptake appeared on rib cage, spine and pelvis. These images suggested a diffuse metastatic disease of the skeleton. The single photon emission computerized tomography guided by computerized tomography (SPECT/CT), centered on lumbar spine, pelvis and the upper end of femurs showed that the multiple hot spots were infact bone fractures. These findings pointed diagnosis to a metabolic disease. The clinical context was in favour of an osteomalacia. Further explorations showed an osteomalacia related to phosphate diabetes. A thorough work-up did not reveal any known aetiology. To date, idiopathic phosphate diabetes seems the most likely diagnosis. Nuclear medicine input in osteomalacia is discussed. 相似文献
5.
Peptide 19-28, a model of an antigenic region of Androctonus australis Hector toxin II, has a rigid alpha-helix structure in the native protein. It was used as immunogen either in the free form, or bound to bovine serum albumin (BSA) or linked to its synthesis support (macroporous polyacrylamide resin). Only the anti-(peptide-BSA) and the anti-(peptide-resin) antibodies recognized the native toxin. The use of short synthetic analogues of peptide 19-28 suggests a specificity difference in the two antipeptides. Anti-(peptide-BSA) recognizes probably two determinants localized at the C and N terminals of the peptide chain. Anti-(peptide-resin) preferentially recognizes the N-terminal extremity. Finally we showed that the alpha-helix region remains accessible to antipeptide 19-28 when the toxin is bound to its receptor. 相似文献
6.
Large fragments of nef-protein and gp110 envelope glycoprotein from HIV-1. Synthesis, CD analysis and immunoreactivity 总被引:1,自引:0,他引:1
J M Sabatier G Fontan E Loret K Mabrouk H Rochat J C Gluckman L Montagnier C Granier E Bahraoui J Van Rietschoten 《International journal of peptide and protein research》1990,35(1):63-72
Chemical synthesis of large peptide fragments (from 18 to 66 amino acid residues long) of the gp110 envelope glycoprotein and of nef-protein from HIV-1 was achieved by the solid phase method. Stepwise assembling of the peptide chains was carried out automatically on 4-(oxymethyl)-phenylacetamidomethyl resin using the N-alpha-butyloxycarbonyl amino acids with benzyl-based side chain protecting groups. Two elongation protocols were used depending on the peptide chain length: a standard cycle, mainly characterized by a single coupling step (Boc-amino acid symmetrical anhydride in dimethylformamide), and an optimized one for large peptides, based on a double coupling strategy (Boc-amino acid symmetrical anhydride first in dimethylformamide, then in dichloromethane). Final cleavage of the peptide from the solid support was carried out by anhydrous hydrogen fluoride and crude peptides were purified by C18 reverse phase medium pressure liquid chromatography after molecular filtration. Characterization of the purified peptides was done by analytical HPLC, amino acid content determination, and circular dichroism analysis both in polar (H2O) and in non-polar (TFE) environments. Immunoreactivity of anti-nef positive sera from HIV-1 infected patients by ELISA with the synthetic peptides was investigated. The results showed four major antigenic regions of nef-protein and mainly the immunodominance of the N- and C-termini of the molecule. Several of these peptides should prove to be useful for both diagnosis and vaccination purposes. 相似文献
7.
A 70 kDa protein of Halobacterium halobium cross-reacts with an antiserum directed against the v-myc gene product of the avian myelocytomatosis virus (MC29). This cross-reaction is in agreement with hybridization studies which indicate that H. halobium possesses DNA and RNA sequences homologous to the v-myc gene. 相似文献
8.
Use of antibodies specific to defined regions of scorpion alpha-toxin to study its interaction with its receptor site on the sodium channel 总被引:2,自引:0,他引:2
Five antibody populations selected by immunoaffinity chromatography for their specificity toward various regions of toxin II of the scorpion Androctonus australis Hector were used to probe the interaction of this protein with its receptor site on the sodium channel. These studies indicate that two antigenic sites, one located around the disulfide bridge 12-63 and one encompassing residues 50-59, are involved in the molecular mechanisms of toxicity neutralization. Fab fragments specific to the region around disulfide bridge 12-63 inhibit binding of the 125I-labeled toxin to its receptor site. Also, these two antigenic regions are inaccessible to their antibodies when the toxin is bound to its receptor site. In contrast, the two other antigenic sites encompassing the only alpha-helix region (residues 23-32) and a beta-turn structure (residues 32-35) are accessible to their respective antibodies when the toxin is bound to its receptor. Together, these data support the recent proposal that a region made of residues that are conserved in the scorpion toxin family is involved in the binding of the toxin to the receptor. 相似文献
9.
Michel Delarue Thierry Darribere Christian Aimar Jean-Claude Boucaut 《Development genes and evolution》1985,194(5):275-280
Summary Most hybrids betweenBufo bufo andB. calamita obtained by nuclear transplantation become arrested at the early gastrula stage. In both parental controls and the hybrid embryos, the presence and distribution of extracellular matrix was analysed with fluorescent wheat germ agglutinin and by immunolabelling with antibodies directed against fibronectin. InB. bufo andB. calamita gastrulae and in the few hybrids that complete gastrulation, the inner surface of the blastocoel roof is covered by a fibronectin-rich fibrillar matrix. In nucleocytoplasmic hybrids whose development was arrested at the gastrula stage, the fibronectin-containing extracellular matrix was either totally absent or poorly developed and disorganized. 相似文献
10.
A Rey B Klein M Rucheton J Caraux D Zagury C Thierry B Serrou 《Cellular immunology》1984,86(1):155-164
Peripheral blood lymphocytes (PBL) of solid-tumor-bearing cancer patients produced a lower interleukin 2 (IL-2) activity after lectin stimulation than did those from normal subjects. Moreover natural killer (NK) cell activity and autologous rosette forming (ARF) cell rate are found significantly correlated with IL-2 production in these patients. No direct relation is observed between ARF cell ratio and NK cell activity in a given patient. A central role for IL-2 in cancer patient immune dysfunctions is suggested. Two lines of pathogenetic mechanisms are documented. First, PBL exhibited cellular function defects, namely, autologous receptor expression, IL-2 production, and NK activity. Second, these dysfunctions involved, at least partly, plasma factors. The possibility of specific deficiency, (e.g., thymic factors) is not documented. Conversely it is demonstrated that patient plasma contain immunosuppressive factor(s) that block(s) IL-2 production and ARF cell expression. Involvement of ARF cell receptor in T-cell activation is discussed. 相似文献