全文获取类型
收费全文 | 1212篇 |
免费 | 89篇 |
国内免费 | 153篇 |
出版年
2024年 | 14篇 |
2023年 | 24篇 |
2022年 | 41篇 |
2021年 | 66篇 |
2020年 | 49篇 |
2019年 | 78篇 |
2018年 | 44篇 |
2017年 | 41篇 |
2016年 | 54篇 |
2015年 | 77篇 |
2014年 | 89篇 |
2013年 | 83篇 |
2012年 | 118篇 |
2011年 | 97篇 |
2010年 | 61篇 |
2009年 | 55篇 |
2008年 | 61篇 |
2007年 | 65篇 |
2006年 | 55篇 |
2005年 | 50篇 |
2004年 | 43篇 |
2003年 | 37篇 |
2002年 | 32篇 |
2001年 | 7篇 |
2000年 | 9篇 |
1999年 | 23篇 |
1998年 | 20篇 |
1997年 | 16篇 |
1996年 | 8篇 |
1995年 | 6篇 |
1994年 | 10篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有1454条查询结果,搜索用时 15 毫秒
71.
Wang Z Petrovic S Mann E Soleimani M 《American journal of physiology. Gastrointestinal and liver physiology》2002,282(3):G573-G579
HCO3(-) secretion is the most important defense mechanism against acid injury in the duodenum. However, the identity of the transporter(s) mediating apical HCO3(-) secretion in the duodenum remains unknown. A family of anion exchangers, which include downregulated in adenoma (DRA or SLC26A3), pendrin (PDS or SLC26A4), and the putative anion transporter (PAT1 or SLC26A6) has recently been identified. DRA and pendrin mediate Cl(-)/base exchange; however, the functional identity and distribution of PAT1 (SLC26A6) is not known. In these studies, we investigated the functional identity, tissue distribution, and membrane localization of PAT1. Expression studies in Xenopus oocytes demonstrated that PAT1 functions in Cl(-)/HCO3(-) exchange mode. Tissue distribution studies indicated that the expression of PAT1 is highly abundant in the small intestine but is low in the colon, a pattern opposite that of DRA. PAT1 was also abundantly detected in stomach and heart. Immunoblot analysis studies identified PAT1 as a approximately 90 kDa protein in the duodenum. Immunohistochemical studies localized PAT1 to the brush border membranes of the villus cells of the duodenum. We propose that PAT1 is an apical Cl(-)/HCO3(-) exchanger in the small intestine. 相似文献
72.
Structural determinants of SecB recognition by SecA in bacterial protein translocation 总被引:1,自引:0,他引:1
SecB is a bacterial chaperone involved in directing pre-protein to the translocation pathway by its specific interaction with the peripheral membrane ATPase SecA. The SecB-binding site on SecA is located at its C terminus and consists of a stretch of highly conserved residues. The crystal structure of SecB in complex with the C-terminal 27 amino acids of SecA from Haemophilus influenzae shows that the SecA peptide is structured as a CCCH zinc-binding motif. One SecB tetramer is bound by two SecA peptides, and the interface involves primarily salt bridges and hydrogen bonding interactions. The structure explains the importance of the zinc-binding motif and conserved residues at the C terminus of SecA in its high-affinity binding with SecB. It also suggests a model of SecB-SecA interaction and its implication for the mechanism of pre-protein transfer in bacterial protein translocation. 相似文献
73.
Zhao G Wan W Mansouri S Alfaro JF Bassler BL Cornell KA Zhou ZS 《Bioorganic & medicinal chemistry letters》2003,13(22):3897-3900
Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme assay and a whole cell quorum sensing assay. The chemical entities of products from the LuxS reaction were also established. Several ribosylhomocysteine analogues have been tested as LuxS inhibitors. 相似文献
74.
Proapoptotic p53-interacting protein 53BP2 is induced by UV irradiation but suppressed by p53 总被引:2,自引:0,他引:2
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)
Lopez CD Ao Y Rohde LH Perez TD O'Connor DJ Lu X Ford JM Naumovski L 《Molecular and cellular biology》2000,20(21):8018-8025
p53 is an important mediator of the cellular stress response with roles in cell cycle control, DNA repair, and apoptosis. 53BP2, a p53-interacting protein, enhances p53 transactivation, impedes cell cycle progression, and promotes apoptosis through unknown mechanisms. We now demonstrate that endogenous 53BP2 levels increase following UV irradiation induced DNA damage in a p53-independent manner. In contrast, we found that the presence of a wild-type (but not mutant) p53 gene suppressed 53BP2 steady-state levels in cell lines with defined p53 genotypes. Likewise, expression of a tetracycline-regulated wild-type p53 cDNA in p53-null fibroblasts caused a reduction in 53BP2 protein levels. However, 53BP2 levels were not reduced if the tetracycline-regulated p53 cDNA was expressed after UV damage in these cells. This suggests that UV damage activates cellular factors that can relieve the p53-mediated suppression of 53BP2 protein. To address the physiologic significance of 53BP2 induction, we utilized stable cell lines with a ponasterone A-regulated 53BP2 cDNA. Conditional expression of 53BP2 cDNA lowered the apoptotic threshold and decreased clonogenic survival following UV irradiation. Conversely, attenuation of endogenous 53BP2 induction with an antisense oligonucleotide resulted in enhanced clonogenic survival following UV irradiation. These results demonstrate that 53BP2 is a DNA damage-inducible protein that promotes DNA damage-induced apoptosis. Furthermore, 53BP2 expression is highly regulated and involves both p53-dependent and p53-independent mechanisms. Our data provide new insight into 53BP2 function and open new avenues for investigation into the cellular response to genotoxic stress. 相似文献
75.
In the nematode Caenorhabditis elegans, animals mutant in the gene encoding the protein product of the unc-45 gene (UNC-45) have disorganized muscle thick filaments in body wall muscles. Although UNC-45 contains tetratricopeptide repeats (TPR) as well as limited similarity to fungal proteins, no biochemical role has yet been found. UNC-45 reporters are expressed exclusively in muscle cells, and a functional reporter fusion is localized in the body wall muscles in a pattern identical to thick filament A-bands. UNC-45 colocalizes with myosin heavy chain (MHC) B in wild-type worms as well as in temperature-sensitive (ts) unc-45 mutants, but not in a mutant in which MHC B is absent. Surprisingly, UNC-45 localization is also not seen in MHC B mutants, in which the level of MHC A is increased, resulting in near-normal muscle thick filament structure. Thus, filament assembly can be independent of UNC-45. UNC-45 shows a localization pattern identical to and dependent on MHC B and a function that appears to be MHC B-dependent. We propose that UNC-45 is a peripheral component of muscle thick filaments due to its localization with MHC B. The role of UNC-45 in thick filament assembly seems restricted to a cofactor for assembly or stabilization of MHC B. 相似文献
76.
77.
78.
长白落叶松激素含量与生长的关系及在早期选择中的应用 总被引:3,自引:2,他引:1
用间接酶联免疫吸附法测定了不同季节不同种源长白落叶松激素含量。结果表明:不同季节长白落叶松的激素含量不同,速生期长白落叶松赤霉素、生长素和细胞分裂素含量高,脱落酸含量低,赤霉素/脱落酸比值大,生长缓慢期测定结果恰好相反。各类激素含量在不同种源长白落叶松间的变异显著,且与生长性状的差异密切相关。生长快的种源赤霉素,细胞分裂素含量高,脱落酸含量低,赤霉素/脱落酸之比大。生长慢的种源则相反。回归分析表明 相似文献
79.
本研究在初步实现水稻原生质体培养的程序化后,选用普通栽培稻P339和特种稻苏御糯选的原生质体为融合亲本,利用碘乙酸(IA)和罗丹明-6G(R-6G)这两个代谢互补抑制剂钝化处理亲本原生质体,确定了合适的抑制条件。P339用0.25mmol/L IA,苏御糯选用50μg/ml R-6G分别经30min钝化处理,通过PEG和高Ca~(2 )、高pH法诱导融合,异源融合体具有代谢互补效应,经培养得到愈伤组织17块,并进一步分化获得不同形态的再生植株12棵。移栽存活的再生植株成熟后可育,通过对这些植株的形态以及酯酶和过氧化物酶同工酶电泳的分析表明是融合后的体细胞杂种植株。 相似文献
80.
Epilepsyisoneofthecommondiseasesduringchildhoodinclinicalpractice.Becauseofcomplexetiology,molecularmechanismsofepileptogenesisarenotfullyclear.Asweknowepilepsyiscausedbyimbalancebetweenexcitationandsuppressionofthebrain.Ithasbeenshowninhumanandanimalm… 相似文献