全文获取类型
收费全文 | 416篇 |
免费 | 31篇 |
出版年
2023年 | 2篇 |
2022年 | 9篇 |
2021年 | 11篇 |
2020年 | 6篇 |
2019年 | 9篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 10篇 |
2015年 | 16篇 |
2014年 | 17篇 |
2013年 | 16篇 |
2012年 | 35篇 |
2011年 | 22篇 |
2010年 | 14篇 |
2009年 | 12篇 |
2008年 | 22篇 |
2007年 | 14篇 |
2006年 | 24篇 |
2005年 | 16篇 |
2004年 | 21篇 |
2003年 | 26篇 |
2002年 | 22篇 |
2001年 | 12篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 9篇 |
1976年 | 4篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 7篇 |
1971年 | 2篇 |
1969年 | 2篇 |
排序方式: 共有447条查询结果,搜索用时 31 毫秒
391.
392.
The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival 总被引:21,自引:0,他引:21
Molyneaux KA Zinszner H Kunwar PS Schaible K Stebler J Sunshine MJ O'Brien W Raz E Littman D Wylie C Lehmann R 《Development (Cambridge, England)》2003,130(18):4279-4286
In mouse embryos, germ cells arise during gastrulation and migrate to the early gonad. First, they emerge from the primitive streak into the region of the endoderm that forms the hindgut. Later in development, a second phase of migration takes place in which they migrate out of the gut to the genital ridges. There, they co-assemble with somatic cells to form the gonad. In vitro studies in the mouse, and genetic studies in other organisms, suggest that at least part of this process is in response to secreted signals from other tissues. Recent genetic evidence in zebrafish has shown that the interaction between stromal cell-derived factor 1 (SDF1) and its G-protein-coupled receptor CXCR4, already known to control many types of normal and pathological cell migrations, is also required for the normal migration of primordial germ cells. We show that in the mouse, germ cell migration and survival requires the SDF1/CXCR4 interaction. First, migrating germ cells express CXCR4, whilst the body wall mesenchyme and genital ridges express the ligand SDF1. Second, the addition of exogenous SDF1 to living embryo cultures causes aberrant germ cell migration from the gut. Third, germ cells in embryos carrying targeted mutations in CXCR4 do not colonize the gonad normally. However, at earlier stages in the hindgut, germ cells are unaffected in CXCR4(-/-) embryos. Germ cell counts at different stages suggest that SDF1/CXCR4 interaction also mediates germ cell survival. These results show that the SDF1/CXCR4 interaction is specifically required for the colonization of the gonads by primordial germ cells, but not for earlier stages in germ cell migration. This demonstrates a high degree of evolutionary conservation of part of the mechanism, but also an area of evolutionary divergence. 相似文献
393.
Membrane binding and relative penetration of indolicidin analogs were studied using lipid/polydiacetylene (PDA) chromatic biomimetic membranes. Colorimetric and fluorescence analyses determined that an indolicidin analog with a proline and tryptophan residue substituted with lysines showed more pronounced bilayer surface interactions, while indolicidin and particularly an indolicidin analog in which all prolines were replaced with alanine residues exhibited deeper insertion into the lipid bilayer. The colorimetric data demonstrated that more pronounced blue-red transitions were observed when the chromatic vesicles incorporated lipopolysaccharide (LPS) within the lipid bilayer, indicating that LPS promoted preferred binding and incorporation of the peptides at the lipid/water interface. The fluorescence quenching experiments further confirmed this outcome. The results indicate that the antibacterial activity of indolicidin most likely requires initial binding to the LPS moieties within bacterial membranes, as well as disruption of the bilayer interface. The degree of hemolysis induced by the analogs, on the other hand, correlated to the extent of penetration into the hydrophobic core of the lipid assembly. 相似文献
394.
Weidinger G Stebler J Slanchev K Dumstrei K Wise C Lovell-Badge R Thisse C Thisse B Raz E 《Current biology : CB》2003,13(16):1429-1434
In most animals, primordial germ cell (PGC) specification and development depend on maternally provided cytoplasmic determinants that constitute the so-called germ plasm. Little is known about the role of germ plasm in vertebrate germ cell development, and its molecular mode of action remains elusive. While PGC specification in mammals occurs via different mechanisms, several germ plasm components required for early PGC development in lower organisms are expressed in mammalian germ cells after their migration to the gonad and are involved in gametogenesis. Here we show that the RNA of dead end, encoding a novel putative RNA binding protein, is a component of the germ plasm in zebrafish and is specifically expressed in PGCs throughout embryogenesis; Dead End protein is localized to perinuclear germ granules within PGCs. Knockdown of dead end blocks confinement of PGCs to the deep blastoderm shortly after their specification and results in failure of PGCs to exhibit motile behavior and to actively migrate thereafter. PGCs subsequently die, while somatic development is not effected. We have identified dead end orthologs in other vertebrates including Xenopus, mouse, and chick, where they are expressed in germ plasm and germ-line cells, suggesting a role in germ-line development in these organisms as well. 相似文献
395.
396.
Agmon I Amit M Auerbach T Bashan A Baram D Bartels H Berisio R Greenberg I Harms J Hansen HA Kessler M Pyetan E Schluenzen F Sittner A Yonath A Zarivach R 《FEBS letters》2004,567(1):20-26
The linkage between internal ribosomal symmetry and transfer RNA (tRNA) positioning confirmed positional catalysis of amino-acid polymerization. Peptide bonds are formed concurrently with tRNA-3' end rotatory motion, in conjunction with the overall messenger RNA (mRNA)/tRNA translocation. Accurate substrate alignment, mandatory for the processivity of protein biosynthesis, is governed by remote interactions. Inherent flexibility of a conserved nucleotide, anchoring the rotatory motion, facilitates chirality discrimination and antibiotics synergism. Potential tRNA interactions explain the universality of the tRNA CCA-end and P-site preference of initial tRNA. The interactions of protein L2 tail with the symmetry-related region periphery explain its conservation and its contributions to nascent chain elongation. 相似文献
397.
Autonomous modes of behavior in primordial germ cell migration 总被引:2,自引:0,他引:2
Zebrafish primordial germ cells (PGCs) are guided toward their targets by the chemokine SDF-1a. PGCs were followed during three phases of their migration: when migrating as individual cells, while remaining in a clustered configuration, and when moving as a cell cluster within the embryo. We found that individually migrating PGCs alternate between migratory and pausing modes. Pausing intervals are characterized by loss of cell polarity and correlate with subsequent changes in the direction of migration. These properties constitute an intrinsic behavior of PGCs, enabling erasure of prior polarity and re-sampling of the environment. Following migration arrest at a site of high SDF-1a levels, PGCs resume migration as a cluster. The seemingly coordinated cluster migration is a result of single-cell movement in response to local variations in SDF-1a distribution. Together, these behavioral modes allow the cells to arrive at specific destinations with high fidelity and remain at their target site. 相似文献
398.
Hydroxymethylglutaryl coenzyme A reductase (HMGCoAR) is required for isoprenoid and cholesterol biosynthesis. In Drosophila, reduced HMGCoAR activity results in germ cell migration defects. We show that pharmacological HMGCoAR inhibition alters zebrafish development and germ cell migration. Embryos treated with atorvastatin (Lipitor) exhibited germ cell migration defects and mild morphologic abnormalities. The effects induced by atorvastatin were completely rescued by prior injection of mevalonate, the product of HMGCoAR activity, or the prenylation precursors farnesol and geranylgeraniol. In contrast, squalene, a cholesterol intermediate further down the pathway, failed to rescue statin-induced defects. Moreover, pharmacologic inhibition of geranylgeranyl transferase 1 (GGT1) protein prenylation activity also resulted in abnormal germ cell migration. Thus, our pharmacological inhibition-and-rescue approach provided detailed information about the elements of isoprenoid biosynthesis that contribute to germ cell migration. Together with data from Drosophila (Santos and Lehmann, this issue), our results highlight a conserved role for protein geranylgeranylation in this context. 相似文献
399.
The continuous growth of the plant embryo is interrupted during the seed maturation processes which results in a dormant seed. The embryo continues development after germination when it grows into a seedling. The embryo growth phase starts after morphogenesis and ends when the embryo fills the seed sac. Very little is known about the processes regulating this phase. We describe mutants that affect embryo growth in two sequential developmental stages. Firstly, embryo growth arrest is regulated by the FUS3/LEC type genes, as mutations in these genes cause a continuation of growth in immature embryos. Secondly, a later stage of embryo dormancy is regulated by ABI3 and abscisic acid; abi3 and aba1 mutants exhibit premature germination only after embryos mature. Mutations affecting both developmental stages result in an additive phenotype and double mutants are highly viviparous. Embryo growth arrest is regulated by cell division activities in both the embryo and the endosperm, which are gradually switched off at the mature embryo stage. In the fus3/lec mutants, however, cell division in both the embryo and endosperm is not arrested, but rather is prolonged throughout seed maturation. Furthermore ectopic cell division occurs in seedlings. Our results indicate that seed dormancy is secured via at least two sequential developmental processes: embryo growth arrest, which is regulated by cell division and embryo dormancy. 相似文献
400.
Cell division activity during apical hook development 总被引:7,自引:0,他引:7
Growth during plant development is predominantly governed by the combined activities of cell division and cell elongation. The relative contribution of both activities controls the growth of a tissue. A fast change in growth is exhibited at the apical hypocotyl of etiolated seedlings where cells grow at different rates to form a hook-like structure, which is traditionally assumed to result from differential cell elongation. Using new tools we show asymmetric distribution of cell division during early stages of hook development. Cell divisions in the apical hook were predominantly found in subepidermal layers during an early step of hook development, but were absent in mutants exhibiting a hookless phenotype. In addition, during exaggeration of hook curvature, which is mediated by ethylene, a rapid change in the combined activities of cell division and cell elongation was detected. Our results indicate a fast change in cell division activity during apical hook development. We suggest that cell division together with cell elongation contributes to apical hook growth. Our results emphasize the change in the relative contribution of cell division and cell elongation in a fast growing structure like the apical hook. 相似文献