全文获取类型
收费全文 | 2193篇 |
免费 | 184篇 |
国内免费 | 154篇 |
出版年
2024年 | 4篇 |
2023年 | 22篇 |
2022年 | 45篇 |
2021年 | 123篇 |
2020年 | 65篇 |
2019年 | 72篇 |
2018年 | 86篇 |
2017年 | 71篇 |
2016年 | 95篇 |
2015年 | 154篇 |
2014年 | 150篇 |
2013年 | 175篇 |
2012年 | 207篇 |
2011年 | 202篇 |
2010年 | 116篇 |
2009年 | 103篇 |
2008年 | 114篇 |
2007年 | 86篇 |
2006年 | 82篇 |
2005年 | 59篇 |
2004年 | 46篇 |
2003年 | 47篇 |
2002年 | 48篇 |
2001年 | 34篇 |
2000年 | 32篇 |
1999年 | 43篇 |
1998年 | 15篇 |
1997年 | 21篇 |
1996年 | 16篇 |
1995年 | 14篇 |
1994年 | 8篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 15篇 |
1990年 | 19篇 |
1989年 | 9篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 12篇 |
1978年 | 9篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1975年 | 9篇 |
1974年 | 6篇 |
1973年 | 3篇 |
1970年 | 5篇 |
排序方式: 共有2531条查询结果,搜索用时 15 毫秒
181.
182.
目的:研究CD1α分子,趋化因子人巨噬细胞炎性蛋白-3α(CCL20/MIP-3α)在宫颈癌组织中的表达及其相关性,探讨其在宫颈癌免疫逃逸机制中的作用。方法:应用免疫组化PV-6000通用二步法检测CD1α和趋化因子CCL20/MIP-3α在正常宫颈组织及宫颈癌组织中的表达,并分析两者之间的相关性。结果:CD1α和CCL20/MIP-3α在宫颈癌中的表达均明显降低(P均0.01);CD1α与CCL20/MIP-3α在宫颈癌中的表达显著相关(P0.01)。结论:在宫颈癌组织中,趋化因子的减少导致抗原提呈细胞数量下降,不足以引起肿瘤局部免疫反应而导致了宫颈局部病变的侵袭及发展。 相似文献
183.
Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker. 相似文献
184.
Qian Jia HongTao Wu XingJun Zhou Jian Gao Wei Zhao JouDi Aziz JingShuang Wei Lihua Hou Shuyin Wu Ying Zhang XiangFeng Dong YanMin Huang WeiYuan Jin HongJie Zhu XinHui Zhao ChunHua Huang LiPing Xing Liwen Li Jun Ma Xiyan Liu Ran Tao ShuaiDong Ye YiGao Song LingLing Song GuanPing Chen ChunLing Du XueTing Zhang Bo Li YanTao Wang Wei Yang Gilbert Rishton YuYang Teng GouQing Leng LuanFeng Li WenXian Liu LiJun Cheng QiuBo Liang ZhengWu Li XiuQin Zhang Yajun Zuo Wei Chen Huicheng Li Matthew Hui 《中国科学:生命科学英文版》2010,53(1):94-100
High mammalian gene expression was obtained for more than twenty different proteins in different cell types by just a few laboratory scale stable gene transfections for each protein. The stable expression vectors were constructed by inserting a naturally-occurring 1.006 kb or a synthetic 0.733 kb DNA fragment (including intron) of extremely GC-rich at the 5′ or/and 3′ flanking regions of these protein genes or their gene promoters. This experiment is the first experimental evidence showing that a non-coding extremely GC-rich DNA fragment is a super “chromatin opening element” and plays an important role in mammalian gene expression. This experiment has further indicated that chromatin-based regulation of mammalian gene expression is at least partially embedded in DNA primary structure, namely DNA GC-content. 相似文献
185.
Teng Y Luo Y Sun X Tu C Xu L Liu W Li Z Christie P 《International journal of phytoremediation》2010,12(5):516-533
A field experiment was conducted to study the effects of inoculation with the arbuscular mycorrhizal fungus Glomus caledonium and/or Rhizobium meliloti on phytoremediation of an agricultural soil contaminated with weathered PCBs by alfalfa grown for 180 days. Planting alfalfa (P), alfalfa inoculated with G. caledonium (P + AM), alfalfa inoculated with R. meliloti (P + R), and alfalfa co-inoculated with R. meliloti and G. caledonium (P+AM+R) decreased significantly initial soil PCB concentrations by 8.1, 12.0, 33.8, and 43.5%, respectively. Inoculation with R. meliloti and/or G. caledonium (P+AM+R) increased the yield of alfalfa, and the accumulation of PCBs in the shoots. Soil microbial counts and the carbon utilization ability of the soil microbial community increased when alfalfa was inoculated with R. meliloti and/or G. caledonium. Results of this field study suggest that synergistic interactions between AMF and Rhizobium may have great potential to enhance phytoremediation by alfalfa of an agricultural soil contaminated with weathered PCBs. 相似文献
186.
The advantages of using traceable fluorescent protein (enhanced green fluorescent protein; EGFP) and a secretory alkaline
phosphatase (SEAP) have been used to generate a reporter gene: the secretory fluorescent protein (SEFP). Sf21 cells, infected
with the recombinant baculovirus containing the SEFP gene, revealed both traceable fluorescence and easily detectable alkaline
phosphatase activity in the culture medium. The distribution of SEFP within the cells revealed that it was excluded from the
nucleus, implying that the accumulation of SEFP in a secretory pathway, similar to that of the secretion signal-tagged FPs.
Furthermore, the time- and dose-dependent release from the blockage of brefeldin A (BFA) confirmed that the secretion of SEFP
was mediated by the secretion pathway and excluded leakage from viral infection. This SEFP reporter gene with traceable fluorescence
and alkaline phosphatase activity may become a useful tool for studies on secretory protein production. 相似文献
187.
Among 21 human strains of Laribacter hongkongensis, small plasmids were observed in four strains, and large ones in six strains. The smallest, 3264-bp plasmid, pHLHK19, has only one ORF that encodes a putative replication initiator protein and a predicted origin of replication (ori) with a DnaA box, three 18-bp direct repeats and five pairs of inverted repeats. An Escherichia coli-L. hongkongensis shuttle vector was constructed by ligating the HindIII-digested pHLHK19, containing the replication initiator protein and ori of pHLHK19, to HindIII-digested pBK-CMV. This shuttle vector can propagate in E. coli and L. hongkongensis with good transformation efficiencies. 相似文献
188.
Feedback inhibition of pantothenate kinase regulates pantothenol uptake by the malaria parasite 总被引:1,自引:0,他引:1
Lehane AM Marchetti RV Spry C van Schalkwyk DA Teng R Kirk K Saliba KJ 《The Journal of biological chemistry》2007,282(35):25395-25405
To survive, the human malaria parasite Plasmodium falciparum must acquire pantothenate (vitamin B5) from the external medium. Pantothenol (provitamin B5) inhibits parasite growth by competing with pantothenate for pantothenate kinase, the first enzyme in the coenzyme A biosynthesis pathway. In this study we investigated pantothenol uptake by P. falciparum and in doing so gained insights into the regulation of the parasite's coenzyme A biosynthesis pathway. Pantothenol was shown to enter P. falciparum-infected erythrocytes via two routes, the furosemide-inhibited "new permeation pathways" induced by the parasite in the infected erythrocyte membrane (the sole access route for pantothenate) and a second, furosemide-insensitive pathway. Having entered the erythrocyte, pantothenol is taken up by the intracellular parasite via a mechanism showing functional characteristics distinct from those of the parasite's pantothenate uptake mechanism. On reaching the parasite cytosol, pantothenol is phosphorylated and thereby trapped by pantothenate kinase, shown here to be under feedback inhibition control by coenzyme A. Furosemide reduced this inherent feedback inhibition by competing with coenzyme A for binding to pantothenate kinase, thereby increasing pantothenol uptake. 相似文献
189.
Respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, encodes a small hydrophobic (SH) protein of unknown function. Parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, also encodes an SH protein, which inhibits tumor necrosis factor alpha (TNF-α) signaling. In this study, recombinant PIV5 viruses without their own SH but containing RSV SH (from RSV strain A2 or B1) in its place (PIV5ΔSH-RSV SH) and RSV lacking its own SH (RSVΔSH) were generated and analyzed. The results indicate that the SH protein of RSV has a function similar to that of PIV5 SH and that it can inhibit TNF-α signaling. 相似文献
190.
Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Zhang S Fei T Zhang L Zhang R Chen F Ning Y Han Y Feng XH Meng A Chen YG 《Molecular and cellular biology》2007,27(12):4488-4499
Smad7 plays an essential role in the negative-feedback regulation of transforming growth factor beta (TGF-beta) signaling by inhibiting TGF-beta signaling at the receptor level. It can interfere with binding to type I receptors and thus activation of receptor-regulated Smads or recruit the E3 ubiquitin ligase Smurf to receptors and thus target them for degradation. Here, we report that Smad7 is predominantly localized in the nucleus of Hep3B cells. The targeted expression of Smad7 in the nucleus conferred superior inhibitory activity on TGF-beta signaling, as determined by reporter assay in mammalian cells and by its effect on zebrafish embryogenesis. Furthermore, Smad7 repressed Smad3/4-, Smad2/4-, and Smad1/4-enhanced reporter gene expression, indicating that Smad7 can function independently of type I receptors. An oligonucleotide precipitation assay revealed that Smad7 can specifically bind to the Smad-responsive element via its MH2 domain, and DNA-binding activity was further confirmed in vivo with the promoter of PAI-1, a TGF-beta target gene, by chromatin immunoprecipitation. Finally, we provide evidence that Smad7 disrupts the formation of the TGF-beta-induced functional Smad-DNA complex. Our findings suggest that Smad7 inhibits TGF-beta signaling in the nucleus by a novel mechanism. 相似文献