全文获取类型
收费全文 | 1474篇 |
免费 | 113篇 |
国内免费 | 3篇 |
专业分类
1590篇 |
出版年
2023年 | 16篇 |
2022年 | 12篇 |
2021年 | 18篇 |
2020年 | 10篇 |
2019年 | 18篇 |
2018年 | 47篇 |
2017年 | 23篇 |
2016年 | 43篇 |
2015年 | 91篇 |
2014年 | 92篇 |
2013年 | 99篇 |
2012年 | 102篇 |
2011年 | 116篇 |
2010年 | 69篇 |
2009年 | 59篇 |
2008年 | 91篇 |
2007年 | 83篇 |
2006年 | 65篇 |
2005年 | 65篇 |
2004年 | 60篇 |
2003年 | 58篇 |
2002年 | 38篇 |
2001年 | 14篇 |
2000年 | 16篇 |
1999年 | 19篇 |
1997年 | 6篇 |
1992年 | 16篇 |
1991年 | 21篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 23篇 |
1987年 | 15篇 |
1986年 | 15篇 |
1985年 | 23篇 |
1984年 | 13篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 13篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 8篇 |
1975年 | 3篇 |
1974年 | 7篇 |
1973年 | 11篇 |
1972年 | 8篇 |
1971年 | 6篇 |
1970年 | 7篇 |
1965年 | 3篇 |
排序方式: 共有1590条查询结果,搜索用时 15 毫秒
61.
62.
Julie Jaquiéry Claude Rispe Denis Roze Fabrice Legeai Ga?l Le Trionnaire Solenn Stoeckel Lucie Mieuzet Corinne Da Silva Julie Poulain Nathalie Prunier-Leterme Béatrice Ségurens Denis Tagu Jean-Christophe Simon 《PLoS genetics》2013,9(8)
Evolutionary theory predicts that sexually antagonistic mutations accumulate differentially on the X chromosome and autosomes in species with an XY sex-determination system, with effects (masculinization or feminization of the X) depending on the dominance of mutations. Organisms with alternative modes of inheritance of sex chromosomes offer interesting opportunities for studying sexual conflicts and their resolution, because expectations for the preferred genomic location of sexually antagonistic alleles may differ from standard systems. Aphids display an XX/X0 system and combine an unusual inheritance of the X chromosome with the alternation of sexual and asexual reproduction. In this study, we first investigated theoretically the accumulation of sexually antagonistic mutations on the aphid X chromosome. Our results show that i) the X is always more favourable to the spread of male-beneficial alleles than autosomes, and should thus be enriched in sexually antagonistic alleles beneficial for males, ii) sexually antagonistic mutations beneficial for asexual females accumulate preferentially on autosomes, iii) in contrast to predictions for standard systems, these qualitative results are not affected by the dominance of mutations. Under the assumption that sex-biased gene expression evolves to solve conflicts raised by the spread of sexually antagonistic alleles, one expects that male-biased genes should be enriched on the X while asexual female-biased genes should be enriched on autosomes. Using gene expression data (RNA-Seq) in males, sexual females and asexual females of the pea aphid, we confirm these theoretical predictions. Although other mechanisms than the resolution of sexual antagonism may lead to sex-biased gene expression, we argue that they could hardly explain the observed difference between X and autosomes. On top of reporting a strong masculinization of the aphid X chromosome, our study highlights the relevance of organisms displaying an alternative mode of sex chromosome inheritance to understanding the forces shaping chromosome evolution. 相似文献
63.
Using event-related fMRI in a sample of 42 healthy participants, we compared the cerebral activity maps obtained when classifying spoken sentences based on the mental content of the main character (belief, deception or empathy) or on the emotional tonality of the sentence (happiness, anger or sadness). To control for the effects of different syntactic constructions (such as embedded clauses in belief sentences), we subtracted from each map the BOLD activations obtained during plausibility judgments on structurally matching sentences, devoid of emotions or ToM. The obtained theory of mind (ToM) and emotional speech comprehension networks overlapped in the bilateral temporo-parietal junction, posterior cingulate cortex, right anterior temporal lobe, dorsomedial prefrontal cortex and in the left inferior frontal sulcus. These regions form a ToM network, which contributes to the emotional component of spoken sentence comprehension. Compared with the ToM task, in which the sentences were enounced on a neutral tone, the emotional sentence classification task, in which the sentences were play-acted, was associated with a greater activity in the bilateral superior temporal sulcus, in line with the presence of emotional prosody. Besides, the ventromedial prefrontal cortex was more active during emotional than ToM sentence processing. This region may link mental state representations with verbal and prosodic emotional cues. Compared with emotional sentence classification, ToM was associated with greater activity in the caudate nucleus, paracingulate cortex, and superior frontal and parietal regions, in line with behavioral data showing that ToM sentence comprehension was a more demanding task. 相似文献
64.
François Binet Gaëlle Mawambo Nicholas Sitaras Nicolas Tetreault Eric Lapalme Sandra Favret Agustin Cerani Dominique Leboeuf Sophie Tremblay Flavio Rezende Aimee M. Juan Andreas Stahl Jean-Sebastien Joyal Éric Milot Randal J. Kaufman Martin Guimond Timothy E. Kennedy Przemyslaw Sapieha 《Cell metabolism》2013,17(3):353-371
Highlights? Canonical ER stress pathways are activated in central neurons during hypoxia/ischemia ? The ER stress endoribonuclease IRE1α degrades the neurovascular guidance cue netrin-1 ? Neuronal-derived netrin-1 activates a reparative proangiogenic program in microglial cells ? Neuronal ER stress prevents reparative angiogenesis in the ischemic neural retina 相似文献
65.
Jacques Danielle Bkaily Ghassan Jasmin Gaétan Ménard Daniel Proschek Libuse 《Molecular and cellular biochemistry》1997,176(1-2):249-256
Using the whole-cell voltage-clamp technique, early embryonic tetrodotoxin (TTX) and Mn2+-insensitive slow Na+ current was detected in 10-22 week old fetal human heart cells as well as in 1-day-old and young cardiomyopathic hamster myocytes. This slow Na+ current in both heart cell preparations has the same kinetics and pharmacology. This type of slow Na+ current was absent in heart cells of newborn and young normal hamsters and became less present in myocytes of 19 and 22 week old human heart myocytes. Our results demonstrate that the slow Na+ channel does exist in early fetal human life and this type of channel continues to be functional after birth in myocytes of the hereditary cardiomyopathic hamster. 相似文献
66.
WOX14 promotes bioactive gibberellin synthesis and vascular cell differentiation in Arabidopsis 下载免费PDF全文
Erwan Denis Nadia Kbiri Viviane Mary Gaëlle Claisse Natalia Conde e Silva Martin Kreis Yves Deveaux 《The Plant journal : for cell and molecular biology》2017,90(3):560-572
Procambial and cambial stem cells provide the initial cells that allow the formation of vascular tissues. WOX4 and WOX14 have been shown to act redundantly to promote procambial cell proliferation and differentiation. Gibberellins (GAs), which have an important role in wood formation, also stimulate cambial cell division. Here we show that the loss of WOX14 function phenocopies some traits of GA‐deficient mutants that can be complemented by exogenous GA application, whereas WOX14 overexpression stimulates the expression of GA3ox anabolism genes and represses GA2ox catabolism genes, promoting the accumulation of bioactive GA. More importantly, our data clearly indicate that WOX14 but not WOX4 promotes vascular cell differentiation and lignification in inflorescence stems of Arabidopsis. 相似文献
67.
Dobrikov MI Gaĭdamakov SA Gaĭnutdinov TI Tenetova ED Shishkin GV Vlasov VV 《Bioorganicheskaia khimiia》1999,25(1):31-39
The photomodification of single-stranded DNA sensitized to visible light (450-580 nm) by a binary system of oligonucleotide conjugates complementary to adjacent DNA sequences was studied. One oligonucleotide carries a residue of the photoreagent p-azidotetrafluorobenzaldehyde hydrazone at its 3'-terminal phosphate, and the other has a residue of the sensitizer, perylene or 1,2-benzanthracene, at the 5'-terminal phosphate. The rate of photomodification sensitized by the perylene derivative is 300,000-fold higher than the rate of photomodification in the absence of the sensitizer. Since the excitation energy of perylene is lower than the energy necessary for the initiation of azide photodecomposition, it is likely that the sensitization in the complementary complex occurs by electron transfer from the azido group of the photoreagent to the excited sensitizer. The sensitization by the 1,2-benzanthracene oligonucleotide derivative occurs by means of singlet-singlet energy transfer, which enables this sensitizer to act as a unconsumable catalyst each molecule of which is able to initiate the photomodification of more than 20 DNA molecules. By both mechanisms, the photomodification occurs with high specificity on the G11 residue of the target DNA. The degree of sensitized photomodification reaches 72%. 相似文献
68.
Bouchet BP Fauvet F Grelier G Galmarini CM Puisieux A 《European journal of cell biology》2011,90(8):631-641
Despite its frequent inactivation in human breast cancers, the role of p21(Cip1) (p21) in morphological plasticity of normal mammary epithelial cells is still poorly understood. To address this question, we have investigated the consequences of p21 silencing in two-dimensional (2D) morphogenesis of untransformed human mammary epithelial cells. Here we show that p21 inactivation causes a reduction of 2D cell spreading and suppresses focal adhesion. In order to investigate the cytoskeletal modifications associated with this altered morphology, we have analyzed the microtubule dynamics in interphase p21-depleted cells. Our results demonstrate that interphase microtubule dynamic instability is strongly increased by p21 silencing. This alteration correlates with severe microtubule hypoacetylation. Next, we show that these microtubule defects in p21-depleted cells can be reversed by the use of the small molecule tubacin, a specific inhibitor of the α-tubulin deacetylase HDAC6. Tubacin-induced microtubule dynamics decrease also correlates with a partial recovery of cell spreading and focal adhesion in those cells. Collectively, these data indicate that p21 regulates the morphological plasticity of normal mammary epithelial cells by modulating dynamics of key cytoskeletal components. 相似文献
69.
Abouzeid H Boisset G Favez T Youssef M Marzouk I Shakankiry N Bayoumi N Descombes P Agosti C Munier FL Schorderet DF 《American journal of human genetics》2011,(1):773-98
Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, not linked to the 10p11.23 locus, whose two affected children have a homozygous mutation in SMOC1. Knockdown experiments of the zebrafish smoc1 revealed that smoc1 is important in eye development and that it is expressed in many organs, including brain and somites. 相似文献
70.
Salin-Cantegrel A Rivière JB Shekarabi M Rasheed S Dacal S Laganière J Gaudet R Rochefort D Lesca G Gaspar C Dion PA Lapointe JY Rouleau GA 《The Journal of biological chemistry》2011,286(32):28456-28465
Missense and protein-truncating mutations of the human potassium-chloride co-transporter 3 gene (KCC3) cause hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), which is a severe neurodegenerative disease characterized by axonal dysfunction and neurodevelopmental defects. We previously reported that KCC3-truncating mutations disrupt brain-type creatine kinase-dependent activation of the co-transporter through the loss of its last 140 amino acids. Here, we report a novel and more distal HMSN/ACC-truncating mutation (3402C → T; R1134X) that eliminates only the last 17 residues of the protein. This small truncation disrupts the interaction with brain-type creatine kinase in mammalian cells but also affects plasma membrane localization of the mutant transporter. Although it is not truncated, the previously reported HMSN/ACC-causing 619C → T (R207C) missense mutation also leads to KCC3 loss of function in Xenopus oocyte flux assay. Immunodetection in Xenopus oocytes and in mammalian cultured cells revealed a decreased amount of R207C at the plasma membrane, with significant retention of the mutant proteins in the endoplasmic reticulum. In mammalian cells, curcumin partially corrected these mutant protein mislocalizations, with more protein reaching the plasma membrane. These findings suggest that mis-trafficking of mutant protein is an important pathophysiological feature of HMSN/ACC causative KCC3 mutations. 相似文献