全文获取类型
收费全文 | 1225篇 |
免费 | 92篇 |
出版年
2024年 | 2篇 |
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 12篇 |
2020年 | 15篇 |
2019年 | 16篇 |
2018年 | 19篇 |
2017年 | 23篇 |
2016年 | 34篇 |
2015年 | 43篇 |
2014年 | 52篇 |
2013年 | 67篇 |
2012年 | 105篇 |
2011年 | 85篇 |
2010年 | 45篇 |
2009年 | 45篇 |
2008年 | 97篇 |
2007年 | 98篇 |
2006年 | 75篇 |
2005年 | 71篇 |
2004年 | 62篇 |
2003年 | 63篇 |
2002年 | 50篇 |
2001年 | 25篇 |
2000年 | 34篇 |
1999年 | 19篇 |
1998年 | 24篇 |
1997年 | 14篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 16篇 |
1993年 | 11篇 |
1992年 | 3篇 |
1991年 | 8篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有1317条查询结果,搜索用时 15 毫秒
131.
Houtani T Munemoto Y Kase M Sakuma S Tsutsumi T Sugimoto T 《Biochemical and biophysical research communications》2005,335(2):277-285
An orphan receptor of ligand-gated ion-channel type (L2, also termed ZAC according to the presence of zinc ion for channel activation) was identified by computer-assisted search programs on human genome database. The L2 protein shares partial homology with serotonin receptors 5HT3A and 5HT3B. We have cloned L2 cDNA derived from human caudate nucleus and characterized the exon-intron structure as follows: (1) The L2 protein has four transmembrane regions (M1-M4) and a long cytoplasmic loop between M3 and M4. (2) The sequence is conserved in species including chimpanzee, dog, cow, and opossum. (3) Nine exons form its protein-coding region and especially exon 5 corresponds to a disulfide bond region on the amino-terminal side. Our analysis using multiple tissue cDNA panels revealed that at least two splicing variants of L2 mRNA are present. The cDNA PCR amplification study revealed that L2 mRNA is expressed in tissues including brain, pancreas, liver, lung, heart, kidney, and skeletal muscle while 5HT3A mRNA could be detected in brain, heart, placenta, lung, kidney, pancreas, and skeletal muscle, and 5HT3B mRNA in brain, kidney, and skeletal muscle, suggesting different significance in tissue expression of these receptors. Regional expression of L2 mRNA and protein was examined in brain. The RT-PCR studies confirmed L2 mRNA expression in hippocampus, striatum, amygdala, and thalamus in adult brain. The L2 protein was immunolocalized by using antipeptide antibodies. Immunostained tissue sections revealed that L2-like immunoreactivity was dominantly expressed in the hippocampal CA3 pyramidal cells and in the polymorphic layer of the dentate gyrus. We analyzed the expression of L2 protein in HEK293 cells using GFP fusion protein reporter system. Western blots revealed that L2 protein confers sugar chains on the extracellular side. In transfected HEK293 cells, cellular membranes and intracellular puncta were densely labeled with GFP, suggesting selective dispatch to the final destination. 相似文献
132.
We examined the antigenicity of an immunomodulatory protein, major membrane protein (MMP)-II, from Mycobacterium leprae, since host defense against M. leprae largely depends on adaptive immunity. Both unprimed and memory T cells from healthy individuals were stimulated by autologous MMP-II-pulsed monocyte-derived dendritic cells (DCs) to produce IFN-gamma. The DC-mediated IFN-gamma production was dependent on the expression of MHC, CD86, and MMP-II antigens. Memory T cells from paucibacillary (PB) leprosy more extensively responded to MMP-II-pulsed DCs than T cells from healthy individuals, while comparable IFN-gamma was produced by unprimed T cells. Memory T cells from multibacillary leprosy, which are normally believed to be anergic, were activated similarly to those from healthy individuals by MMP-II-pulsed DCs. These results suggest that memory T cells from PB leprosy are primed with MMP-II prior to the manifestation of the disease, and MMP-II is highly antigenic in terms of activation of adaptive immunity. 相似文献
133.
Taniwaki T Haruna K Nakamura H Sekimoto T Oike Y Imaizumi T Saito F Muta M Soejima Y Utoh A Nakagata N Araki M Yamamura K Araki K 《Development, growth & differentiation》2005,47(3):163-172
We have developed a new exchangeable gene trap vector, pU-17, carrying the intron-lox71-splicing acceptor (SA)-beta geo-loxP-pA-lox2272-pSP73-lox511. The SA contains three stop codons in-frame with the ATG of beta galactosidase/neomycin-resistance fusion gene (beta geo) that can function in promoter trapping. We found that the trap vector was highly selective for integrations in the introns adjacent to the exon containing the start codon. Furthermore, by using the Cre-mutant lox system, we successfully replaced the beta geo gene with the enhanced green fluorescent protein (EGFP) gene, established mouse lines with the replaced clones, removed the selection marker gene by mating with Flp-deleter mice, and confirmed that the replaced EGFP gene was expressed in the same pattern as the beta geo gene. Thus, using this pU-17 trap vector, we can initially carry out random mutagenesis, and then convert it to a gain-of-function mutation by replacing the beta geo gene with any gene of interest to be expressed under the control of the trapped promoter through Cre-mediated recombination. 相似文献
134.
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
135.
Yanagi K Mizuno T Tsuyama T Tada S Iida Y Sugimoto A Eki T Enomoto T Hanaoka F 《The Journal of biological chemistry》2005,280(20):19689-19694
Cdt1 is an essential component for the assembly of a pre-replicative complex. Cdt1 activity is inhibited by geminin, which also participates in neural development and embryonic differentiation in many eukaryotes. Although Cdt1 homologues have been identified in organisms ranging from yeast to human, geminin homologues had not been described for Caenorhabditis elegans and fungi. Here, we identify the C. elegans geminin, GMN-1. Biochemical analysis reveals that GMN-1 associates with C. elegans CDT-1, the Hox protein NOB-1, and the Six protein CEH-32. GMN-1 inhibits not only the interaction between mouse Cdt1 and Mcm6 but also licensing activity in Xenopus egg extracts. RNA interference-mediated reduction of GMN-1 is associated with enlarged germ nuclei with aberrant nucleolar morphology, severely impaired gametogenesis, and chromosome bridging in intestinal cells. We conclude that the Cdt1-geminin system is conserved throughout metazoans and that geminin has evolved in these taxa to regulate proliferation and differentiation by directly interacting with Cdt1 and homeobox proteins. 相似文献
136.
Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart 总被引:11,自引:0,他引:11 下载免费PDF全文
Tomita Y Matsumura K Wakamatsu Y Matsuzaki Y Shibuya I Kawaguchi H Ieda M Kanakubo S Shimazaki T Ogawa S Osumi N Okano H Fukuda K 《The Journal of cell biology》2005,170(7):1135-1146
Arodent cardiac side population cell fraction formed clonal spheroids in serum-free medium, which expressed nestin, Musashi-1, and multi-drug resistance transporter gene 1, markers of undifferentiated neural precursor cells. These markers were lost following differentiation, and were replaced by the expression of neuron-, glial-, smooth muscle cell-, or cardiomyocyte-specific proteins. Cardiosphere-derived cells transplanted into chick embryos migrated to the truncus arteriosus and cardiac outflow tract and contributed to dorsal root ganglia, spinal nerves, and aortic smooth muscle cells. Lineage studies using double transgenic mice encoding protein 0-Cre/Floxed-EGFP revealed undifferentiated and differentiated neural crest-derived cells in the fetal myocardium. Undifferentiated cells expressed GATA-binding protein 4 and nestin, but not actinin, whereas the differentiated cells were identified as cardiomyocytes. These results suggest that cardiac neural crest-derived cells migrate into the heart, remain there as dormant multipotent stem cells-and under the right conditions-differentiate into cardiomyocytes and typical neural crest-derived cells, including neurons, glia, and smooth muscle. 相似文献
137.
Daimon M Kido T Baba M Oizumi T Jimbu Y Kameda W Yamaguchi H Ohnuma H Tominaga M Muramatsu M Kato T 《Biochemical and biophysical research communications》2005,329(1):205-210
To examine the association of the ATP-binding cassette transporter 1 (ABCA1) gene with type 2 diabetes (DM), we studied genetic polymorphisms of the ABCA1 gene including its linkage disequilibrium (LD) and haplotype analyses using a Japanese population. A sample set (DM:72, IGT:75, and NGT:227) was genotyped with 34 SNPs distributed from the promoter region to the last exon of the ABCA1 gene. LD between SNPs was assessed in pairwise manner. Among 13 LD blocks constructed, an LD block at the 5'-region showed a significant difference in the haplotype distribution between the study groups (NGT vs. IGT + DM: overall p = 0.0180; NGT vs. DM: 0.0001). Fisher's exact probability test (NGT vs. DM) showed a significant association of the haplotype 2 of the LD block (p = 0.0001), with an odds ratio (OR) of 2.53 (95%CI:1.62-4.12). Diplotype analysis also showed a significant association of the diplotypes with the haplotype 2 (OR:2.59, 95%CI:1.48-4.54, p = 0.0013). 相似文献
138.
Watanabe Y Hashimoto Y Shiratsuchi A Takizawa T Nakanishi Y 《Biochemical and biophysical research communications》2005,337(3):881-886
Influenza virus-infected cells undergo apoptosis and become susceptible to phagocytosis by macrophages, and this leads to the inhibition of virus propagation in vitro. To assess if this were also true in vivo, mice infected with influenza A/WSN (H1N1) virus were administered with phagocytosis inhibitors and examined for the progress of influenza. Administration of the inhibitors caused a decrease in the level of phagocytosis observed with bronchoalveolar lavage cells. We found that both the lethality in mice and the extent of inflammation in the lung were augmented in those mice. These results suggest that phagocytosis of virus-infected cells helps suppress the progress of influenza in mice. 相似文献
139.
140.