全文获取类型
收费全文 | 3217篇 |
免费 | 267篇 |
国内免费 | 104篇 |
出版年
2024年 | 8篇 |
2023年 | 82篇 |
2022年 | 135篇 |
2021年 | 202篇 |
2020年 | 119篇 |
2019年 | 165篇 |
2018年 | 172篇 |
2017年 | 108篇 |
2016年 | 109篇 |
2015年 | 151篇 |
2014年 | 272篇 |
2013年 | 302篇 |
2012年 | 154篇 |
2011年 | 151篇 |
2010年 | 148篇 |
2009年 | 148篇 |
2008年 | 172篇 |
2007年 | 126篇 |
2006年 | 101篇 |
2005年 | 109篇 |
2004年 | 88篇 |
2003年 | 77篇 |
2002年 | 76篇 |
2001年 | 46篇 |
2000年 | 39篇 |
1999年 | 20篇 |
1998年 | 32篇 |
1997年 | 23篇 |
1996年 | 25篇 |
1995年 | 21篇 |
1994年 | 20篇 |
1993年 | 17篇 |
1992年 | 14篇 |
1991年 | 15篇 |
1990年 | 13篇 |
1989年 | 16篇 |
1988年 | 24篇 |
1987年 | 11篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 9篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1973年 | 2篇 |
排序方式: 共有3588条查询结果,搜索用时 93 毫秒
71.
Zhiguang Zhao Rong Fan Weina Xu Yahui Kou Yangyang Wang Xuehua Ma Zhuo Du 《Molecular systems biology》2021,17(4)
Elucidating the chromatin dynamics that orchestrate embryogenesis is a fundamental question in developmental biology. Here, we exploit position effects on expression as an indicator of chromatin activity and infer the chromatin activity landscape in every lineaged cell during Caenorhabditis elegans early embryogenesis. Systems‐level analyses reveal that chromatin activity distinguishes cellular states and correlates with fate patterning in the early embryos. As cell lineage unfolds, chromatin activity diversifies in a lineage‐dependent manner, with switch‐like changes accompanying anterior–posterior fate asymmetry and characteristic landscapes being established in different cell lineages. Upon tissue differentiation, cellular chromatin from distinct lineages converges according to tissue types but retains stable memories of lineage history, contributing to intra‐tissue cell heterogeneity. However, the chromatin landscapes of cells organized in a left–right symmetric pattern are predetermined to be analogous in early progenitors so as to pre‐set equivalent states. Finally, genome‐wide analysis identifies many regions exhibiting concordant chromatin activity changes that mediate the co‐regulation of functionally related genes during differentiation. Collectively, our study reveals the developmental and genomic dynamics of chromatin activity at the single‐cell level. 相似文献
72.
73.
Aberrant epigenetic alterations play a decisive role in cancer initiation and propagation via the regulation of key tumor suppressor genes and oncogenes or by modulation of essential signaling pathways. Autophagy is a highly regulated mechanism required for the recycling and degradation of surplus and damaged cytoplasmic constituents in a lysosome dependent manner. In cancer, autophagy has a divergent role. For instance, autophagy elicits tumor promoting functions by facilitating metabolic adaption and plasticity in cancer stem cells (CSCs) and cancer cells. Moreover, autophagy exerts pro-survival mechanisms to these cancerous cells by influencing survival, dormancy, immunosurveillance, invasion, metastasis, and resistance to anti-cancer therapies. In addition, recent studies have demonstrated that various tumor suppressor genes and oncogenes involved in autophagy, are tightly regulated via different epigenetic modifications, such as DNA methylation, histone modifications and non-coding RNAs. The impact of epigenetic regulation of autophagy in cancer cells and CSCs is not well-understood. Therefore, uncovering the complex mechanism of epigenetic regulation of autophagy provides an opportunity to improve and discover novel cancer therapeutics. Subsequently, this would aid in improving clinical outcome for cancer patients. In this review, we provide a comprehensive overview of the existing knowledge available on epigenetic regulation of autophagy and its importance in the maintenance and homeostasis of CSCs and cancer cells. 相似文献
74.
75.
温度是限制物种适应性分布的重要环境因子,对极端环境温度的耐受性决定生物分布和扩散范围,而表观遗传可以提供快速的响应机制,促使生物快速适应极端环境温度。染色质重塑作为表观遗传的重要组成部分之一,其可以通过调控胁迫相关基因的表达从而促进生物适应不良环境条件。本文主要阐述了染色质重塑复合物的分类、组成和染色质重塑的方式,梳理了染色质重塑在生物温度适应性中的研究进展,提出染色质重塑在生物适应不良环境温度过程中发挥重要作用,并对未来染色质重塑与温度适应性研究提出建议。 相似文献
76.
ERIC S. BONO PATRICK SMOLINSKI AL CASAGRANDA JUNDE XU 《Computer methods in biomechanics and biomedical engineering》2013,16(2):125-131
The Shear-slip Mesh Update Method (SSMUM) is being used in flow simulations involving large but regular displacements of one or more boundaries of the computational domain. We follow up the earlier discussion of the method with notes on practical implementation aspects. In order to establish a benchmark problem for this class of flow problems, we define and report results from a two-dimensional viscous flow around a rotating stirrer in a square chamber. The application potential of the method is demonstrated in the context of biomedical design problem, as we perform an analysis of blood flow in a centrifugal left ventricular assist device, or blood pump, which involves a rotating impeller in a non-axisymmetric housing. 相似文献
77.
C Rodríguez-Burford D K Oelschlager L I Talley M N Barnes E E Partridge 《Biotechnic & histochemistry》2013,88(1):17-21
We describe here a computational morphology-based approach to the investigation of possible causes of chromatin alterations in sperm. A comprehensive set of state-of-the-art and geometric measures are computationally extracted from toluidine blue stained images and analyzed to infer the possible processes leading to normal and abnormal chromatin formation while seeking a possible taxonomy of chromatin alterations and their influence on sperm head morphology. Using this methodology, we have identified higher chromatin fragility at some specific points of the sperm head. Despite the lack of correlation between morphologies of sperm head and chromatin structure, four main morphological types of chromatin alterations in bull spermatozoa have been identified and their possible causes discussed. 相似文献
78.
Donato Chiatante Gabriella S. Scippa Lucia Maiuro Elisabetta Onelli Giuseppe Patrignani 《Plant biosystems》2013,147(1):35-47
ABSTRACT To understand the mechanisms which enable the nucleus to function under low water potential, the morphology and biochemistry of potato cell nuclei were studied. Conformational modifications were observed in the chromatin of nuclei of cells growing under low water potential. These modifications include a higher number of heterochromatic centres, enlargement of the nuclear diameter, and a different accessibility of DNA to the action of restriction enzymes. Biochemical analyses showed that these chromatin modifications may coincide with quantitative and qualitative variations of several nuclear proteins, some of which may belong to the dehydrin family. We especially focussed our attention on a 45-kDa protein that is heat-stable and is recognised by an antibody raised against the conserved domain of dehydrins. The survival of potato cells in an environment where water availability is low may depend on several simultaneous events regarding the nucleus. The accumulation in the nucleus of specific proteins such as dehydrins could be required to stabilise the chromatin by means of their molecule-salvation action. Further studies are in progress to check whether or not variations in chromatin organisation may be one of the numerous traits that a cell must acquire to become water-stress resistant. 相似文献
79.
80.
Neil Brockdorff 《RNA (New York, N.Y.)》2013,19(4):429-442