全文获取类型
收费全文 | 304篇 |
免费 | 49篇 |
出版年
2021年 | 3篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 4篇 |
2015年 | 10篇 |
2014年 | 3篇 |
2013年 | 8篇 |
2012年 | 8篇 |
2011年 | 8篇 |
2010年 | 5篇 |
2009年 | 7篇 |
2008年 | 12篇 |
2007年 | 13篇 |
2006年 | 10篇 |
2005年 | 12篇 |
2004年 | 24篇 |
2003年 | 18篇 |
2002年 | 16篇 |
2001年 | 11篇 |
2000年 | 20篇 |
1999年 | 19篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 12篇 |
1991年 | 7篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1966年 | 3篇 |
1965年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有353条查询结果,搜索用时 750 毫秒
41.
Hirokawa YS Takagi A Uchida K Kozuka Y Yoneda M Watanabe M Shiraishi T 《Cellular & molecular biology letters》2007,12(3):370-377
In this paper, we describe the isolation and characterization of two PC3 subclones. One subclone, mr, showed an epithelial
phenotype, the other, M1, showed a sarcomatous morphology. Transplanted into nude mice, mr developed tumors at a dramatically
faster rate than M1. Comparing the two subclones, differentially expressed genes were identified, including E-cadherin, IL-8
and STAG1/PMEPA1. These genes were expressed at higher levels in mr than in M1. 相似文献
42.
43.
Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination 总被引:7,自引:0,他引:7
The leftward flow in extraembryonic fluid is critical for the initial determination of the left-right axis of mouse embryos. It is unclear if this is a conserved mechanism among other vertebrates and how the directionality of the flow arises from the motion of cilia. In this paper, we show that rabbit and medakafish embryos also exhibit a leftward fluid flow in their ventral nodes. In all cases, primary monocilia present a clockwise rotational-like motion. Observations of defective ciliary dynamics in mutant mouse embryos support the idea that the posterior tilt of the cilia during rotational-like beating can explain the leftward fluid flow. Moreover, we show that this leftward flow may produce asymmetric distribution of exogenously introduced proteins, suggesting morphogen gradients as a subsequent mechanism of left-right axis determination. Finally, we experimentally and theoretically characterize under which conditions a morphogen gradient can arise from the flow. 相似文献
44.
Microtubule-associated protein 1A (MAP1A) is a high-molecular-weight protein that is comprised of a heavy chain and a light chain (LC2) and is widely distributed along the microtubules in both mature neurons and glial cells. To illustrate the interaction among the MAP1A heavy chain, light chain, and microtubule, we prepared DNA constructs with Myc-, EGFP-, or DsRed-tags for full-length MAP1A DNA expressing whole MAP1A protein, two domains of MAP1A heavy chain, and light chain. Distribution patterns of various MAP1A domains as well as their interactions with microtubules were monitored in a non-neuronal COS7 and a neuronal Neuro2A cells. Our data revealed that a complete MAP1A protein, which contains both heavy chain and LC2, could be colocalized with microtubule networks not only in Neuro2A cells but also in transfected COS7 cells. Filamentous structures failed to be visualized along microtubules in COS7 cells transfected with MAP1A heavy chain or LC2 alone. Whereas, after introducing MAP1A heavy chain with LC2 into COS7 cells, both heavy chain and LC2 could be colocalized with microtubules. From our functional analysis, both MAP1A and its LC2 could protect microtubules against the challenge of nacodazol. Data collected from yeast two-hybrid assays of various MAP1A domains confirmed that the interaction of LC2 and NH2-terminal of MAP1A heavy chain is important for microtubule binding. From our analysis of MAP1A functional domains, we suggest that interactions between MAP1A heavy chain and LC2 are critical for the binding of microtubules. 相似文献
45.
Nodal cilia dynamics and the specification of the left/right axis in early vertebrate embryo development 下载免费PDF全文
Buceta J Ibañes M Rasskin-Gutman D Okada Y Hirokawa N Izpisúa-Belmonte JC 《Biophysical journal》2005,89(4):2199-2209
Nodal cilia dynamics is a key factor for left/right axis determination in mouse embryos through the induction of a leftward fluid flow. So far it has not been clearly established how such dynamics is able to induce the asymmetric leftward flow within the node. Herein we propose that an asymmetric two-phase nonplanar beating cilia dynamics that involves the bending of the ciliar axoneme is responsible for the leftward fluid flow. We support our proposal with a host of hydrodynamic arguments, in silico experiments and in vivo video microscopy data in wild-type embryos and inv mutants. Our phenomenological modeling approach underscores how the asymmetry and speed of the flow depends on different relevant parameters. In addition, we discuss how the combination of internal and external mechanisms might cause the two-phase beating cilia dynamics. 相似文献
46.
Teng J Rai T Tanaka Y Takei Y Nakata T Hirasawa M Kulkarni AB Hirokawa N 《Nature cell biology》2005,7(5):474-482
In the developing brain, the organization of the neuroepithelium is maintained by a critical balance between proliferation and cell-cell adhesion of neural progenitor cells. The molecular mechanisms that underlie this are still largely unknown. Here, through analysis of a conditional knockout mouse for the Kap3 gene, we show that post-Golgi transport of N-cadherin by the KIF3 molecular motor complex is crucial for maintaining this balance. N-cadherin and beta-catenin associate with the KIF3 complex by co-immunoprecipitation, and colocalize with KIF3 in cells. Furthermore, in KAP3-deficient cells, the subcellular localization of N-cadherin was disrupted. Taken together, these results suggest a potential tumour-suppressing activity for this molecular motor. 相似文献
47.
Intracellular transport is fundamental for neuronal morphogenesis, function and survival. Many proteins are selectively transported to either axons or dendrites. In addition, some specific mRNAs are transported to dendrites for local translation. Proteins of the kinesin superfamily participate in selective transport by using adaptor or scaffolding proteins to recognize and bind cargoes. The molecular components of RNA-transporting granules have been identified, and it is becoming clear how cargoes are directed to axons and dendrites by kinesin superfamily proteins. Here we discuss the molecular mechanisms of directional axonal and dendritic transport with specific emphasis on the role of motor proteins and their mechanisms of cargo recognition. 相似文献
48.
Regulation of osteoclastogenesis by three human RANKL isoforms expressed in NIH3T3 cells 总被引:4,自引:0,他引:4
Suzuki J Ikeda T Kuroyama H Seki S Kasai M Utsuyama M Tatsumi M Uematsu H Hirokawa K 《Biochemical and biophysical research communications》2004,314(4):1021-1027
Receptor activator of nuclear factor-kappaB ligand (RANKL) induces osteoclastogenesis by binding with the receptor, receptor activator of nuclear factor-kappaB in the presence of macrophage colony-stimulating factor. Three human RANKL isoforms, hRANKL1, hRANKL2, and hRANKL3, were identified. hRANKL1 was identical to previously reported RANKL and possessed intracellular, transmembrane, and extracellular domains, hRANKL2 did not have the intracellular domain, and hRANKL3 did not have the intracellular and transmembrane domains. When bone marrow macrophages were cultured with NIH3T3 cells expressing hRANKL1, osteoclasts were formed, but when cultured with NIH3T3 cells expressing hRANKL2 or hRANKL3, no tartrate resistant acid phosphatase-positive cell was observed. In the coculture system, coexpression of hRANKL3 with hRANKL1 significantly inhibited the formation of osteoclasts by hRANKL1, but coexpression of hRANKL2 with hRANKL1 did not affect the osteoclastogenesis by hRANKL1 significantly. These results suggest that the activity of osteoclastogenesis by hRANKL1 is regulated by the attenuator, hRANKL3. 相似文献
49.
A standardized kinesin nomenclature 总被引:28,自引:0,他引:28
Lawrence CJ Dawe RK Christie KR Cleveland DW Dawson SC Endow SA Goldstein LS Goodson HV Hirokawa N Howard J Malmberg RL McIntosh JR Miki H Mitchison TJ Okada Y Reddy AS Saxton WM Schliwa M Scholey JM Vale RD Walczak CE Wordeman L 《The Journal of cell biology》2004,167(1):19-22
In recent years the kinesin superfamily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized kinesin nomenclature based on 14 family designations. The scheme unifies all previous phylogenies and nomenclature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered. 相似文献
50.
Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor 总被引:2,自引:0,他引:2
Satoh T Moroi R Aritake K Urade Y Kanai Y Sumi K Yokozeki H Hirai H Nagata K Hara T Utsuyama M Hirokawa K Sugamura K Nishioka K Nakamura M 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(4):2621-2629
PGD(2) plays roles in allergic inflammation via specific receptors, the PGD receptor designated DP and CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells). We generated mutant mice carrying a targeted disruption of the CRTH2 gene to investigate the functional roles of CRTH2 in cutaneous inflammatory responses. CRTH2-deficent mice were fertile and grew normally. Ear-swelling responses induced by hapten-specific IgE were less pronounced in mutant mice, giving 35-55% of the responses of normal mice. Similar results were seen in mice treated with a hemopoietic PGD synthase inhibitor, HQL-79, or a CRTH2 antagonist, ramatroban. The reduction in cutaneous responses was associated with decreased infiltration of lymphocytes, eosinophils, and basophils and decreased production of macrophage-derived chemokine and RANTES at inflammatory sites. In models of chronic contact hypersensitivity induced by repeated hapten application, CRTH2 deficiency resulted in a reduction by approximately half of skin responses and low levels (63% of control) of serum IgE production, although in vivo migration of Langerhans cells and dendritic cells to regional lymph nodes was not impaired in CRTH2-deficient mice. In contrast, delayed-type hypersensitivity to SRBC and irritation dermatitis in mutant mice were the same as in wild-type mice. These findings indicate that the PGD(2)-CRTH2 system plays a significant role in chronic allergic skin inflammation. CRTH2 may represent a novel therapeutic target for treatment of human allergic disorders, including atopic dermatitis. 相似文献