全文获取类型
收费全文 | 7282篇 |
免费 | 368篇 |
国内免费 | 8篇 |
出版年
2023年 | 13篇 |
2022年 | 32篇 |
2021年 | 71篇 |
2020年 | 43篇 |
2019年 | 67篇 |
2018年 | 98篇 |
2017年 | 86篇 |
2016年 | 119篇 |
2015年 | 199篇 |
2014年 | 254篇 |
2013年 | 523篇 |
2012年 | 428篇 |
2011年 | 444篇 |
2010年 | 282篇 |
2009年 | 287篇 |
2008年 | 470篇 |
2007年 | 476篇 |
2006年 | 446篇 |
2005年 | 510篇 |
2004年 | 492篇 |
2003年 | 460篇 |
2002年 | 424篇 |
2001年 | 78篇 |
2000年 | 71篇 |
1999年 | 70篇 |
1998年 | 102篇 |
1997年 | 77篇 |
1996年 | 86篇 |
1995年 | 84篇 |
1994年 | 59篇 |
1993年 | 65篇 |
1992年 | 66篇 |
1991年 | 56篇 |
1990年 | 51篇 |
1989年 | 44篇 |
1988年 | 38篇 |
1987年 | 49篇 |
1986年 | 34篇 |
1985年 | 35篇 |
1984年 | 46篇 |
1983年 | 33篇 |
1982年 | 42篇 |
1981年 | 35篇 |
1980年 | 24篇 |
1979年 | 34篇 |
1978年 | 28篇 |
1977年 | 20篇 |
1976年 | 25篇 |
1973年 | 14篇 |
1970年 | 11篇 |
排序方式: 共有7658条查询结果,搜索用时 15 毫秒
991.
Miyazaki T Takenaka T Inoue T Sato M Miyajima Y Nodera M Hanyu M Ohno Y Shibazaki S Suzuki H 《Biological trace element research》2012,145(3):375-381
Zinc deficiency leads to decreased cellular immune responses. The overproduction of nitrogen species derived from inducible
nitric oxide synthase (iNOS), its enzyme, and interleukine-1 beta (IL-1β), and inflammatory cytokine have been implicated
in immune responses. The goal of this study was to investigate the effects of lipopolysaccharide (LPS)-induced changes in
NO metabolites, iNOS, and IL-1β protein expression in the lungs of zinc-deficient rats. Male Sprague–Dawley rats (body weight,
100 g) were divided into two groups and were fed either a zinc-deficient diet (ZnD) or a zinc-containing diet (Cont). After
4 weeks on these diets, rats received a 10-mg/kg dose of LPS injected via the tail vein and were then maintained for an additional
72 h. To determine total NO concentrations in the blood, serum zinc concentration, iNOS protein expression, IL-1β, and iNOS
immunohistochemistry, blood and lung samples were obtained at pre-LPS injection, 5, 24, and 72 h after injection. Total NO
levels were significantly increased at 5, at 24, and at 72 h after LPS injection compared with pre-LPS injection level in
ZnD group; significant changes in total NO levels was elevated at 5 h from at pre-LPS level but not significant changes from
basal level at 24 and 72 h in the control group. Based on western blot analyses and immunohistochemistry, clear bands indicating
iNOS and IL-1β protein expression and iNOS antibody-stained inflammatory cells were detected at 5 and 24 h in the ZnD group
and 5 h in the Cont group, not observed at 24 and 72 h in the control group. These results suggest that zinc deficiency induces
overexpression of iNOS and IL-1β proteins from inflammatory cells around the alveolar blood vessels, resulting in overproduction
of total NO and persisted inflammatory response in the zinc-deficient rat lung. Taken together, overexpression of LPS-induced
iNOS, overproduction of iNOS-derived NO, and overexpression of IL-1β may induce nitrosative and oxidative stresses in the
lung, and these stresses may be involved low immunity of zinc deficiency states. 相似文献
992.
993.
Kayama S Shigemoto N Kuwahara R Onodera M Yokozaki M Ohge H Kato F Hisatsune J Sugai M 《Journal of microbiological methods》2012,88(1):182-184
Klebsiella pneumoniae resistant to almost all ß-lactams except imipenem designated as ISMRK (imipenem-susceptible meropenem-resistant Klebsiella) is emerging in Japan. All ISMRK carries blaIMP-6 which differs from blaIMP-1 by only a single nucleotide at position 640. We devised a rapid detection system of blaIMP-6 by using ARMS PCR. 相似文献
994.
K Sato M Ishiai K Toda S Furukoshi A Osakabe H Tachiwana Y Takizawa W Kagawa H Kitao N Dohmae C Obuse H Kimura M Takata H Kurumizaka 《The EMBO journal》2012,31(17):3524-3536
Fanconi anaemia (FA) is a rare hereditary disorder characterized by genomic instability and cancer susceptibility. A key FA protein, FANCD2, is targeted to chromatin with its partner, FANCI, and plays a critical role in DNA crosslink repair. However, the molecular function of chromatin-bound FANCD2-FANCI is still poorly understood. In the present study, we found that FANCD2 possesses nucleosome-assembly activity in vitro. The mobility of histone H3 was reduced in FANCD2-knockdown cells following treatment with an interstrand DNA crosslinker, mitomycin C. Furthermore, cells harbouring FANCD2 mutations that were defective in nucleosome assembly displayed impaired survival upon cisplatin treatment. Although FANCI by itself lacked nucleosome-assembly activity, it significantly stimulated FANCD2-mediated nucleosome assembly. These observations suggest that FANCD2-FANCI may regulate chromatin dynamics during DNA repair. 相似文献
995.
Liu N Matsumoto M Kitagawa K Kotake Y Suzuki S Shirasawa S Nakayama KI Nakanishi M Niida H Kitagawa M 《The EMBO journal》2012,31(10):2365-2377
The tumour suppressor gene product Mig-6 acts as an inhibitor of epidermal growth factor (EGF) signalling. However, its posttranslational modifications and regulatory mechanisms have not been elucidated. Here, we investigated the phosphorylation of human Mig-6 and found that Chk1 phosphorylated Mig-6 in vivo as well as in vitro. Moreover, EGF stimulation promoted phosphorylation of Mig-6 without DNA damage and the phosphorylation was inhibited by depletion of Chk1. EGF also increased Ser280-phosphorylated Chk1, a cytoplasmic-tethering form, via PI3K pathway. Mass spectrometric analyses suggested that Ser 251 of Mig-6 was a major phosphorylation site by Chk1 in vitro and in vivo. Substitution of Ser 251 to alanine increased inhibitory activity of Mig-6 against EGF receptor (EGFR) activation. Moreover, EGF-dependent activation of EGFR and cell growth were inhibited by Chk1 depletion, and were rescued by co-depletion of Mig-6. Our results suggest that Chk1 phosphorylates Mig-6 on Ser 251, resulting in the inhibition of Mig-6, and that Chk1 acts as a positive regulator of EGF signalling. This is a novel function of Chk1. 相似文献
996.
Sakurai T Lee H Kashima M Saito Y Hayashi T Kudome-Takamatsu T Nishimura O Agata K Shibata N 《The International journal of developmental biology》2012,56(1-3):173-182
The growth in size of freshwater planarians in response to nutrient intake is limited by the eventual separation of tail and body fragments in a process called fission. The resulting tail fragment regenerates the entire body as an artificially amputated tail fragment would do, and the body fragment regenerates a tail, resulting in two whole planarians. This regenerative ability is supported by pluripotent somatic stem cells, called neoblasts, which are distributed throughout almost the entire body of the planarian. Neoblasts are the only planarian cells with the ability to continuously proliferate and give rise to all types of cells during regeneration, asexual reproduction, homeostasis, and growth. In order to investigate the molecular characteristics of neoblasts, we conducted an extensive search for neoblast-specific genes using the High Coverage Expression Profiling (HiCEP) method, and tested the function of the resulting candidates by RNAi. Disruption of the expression of one candidate gene, DjP2X-A (Dugesia japonica membrane protein P2X homologue), resulted in a unique phenotype. DjP2X-A RNAi leads to an increase of fission events upon feeding. We confirmed by immunohistochemistry that DjP2X-A is a membrane protein, and elucidated its role in regulating neoblast proliferation, thereby explaining its unique phenotype. We found that DjP2X-A decreases the burst of neoblast proliferation that normally occurs after feeding. We also found that DjP2X-A is required for normal proliferation in starved animals. We propose that DjP2X-A modulates stem cell proliferation in response to the nutritional condition. 相似文献
997.
998.
Goetz R Ohnishi M Ding X Kurosu H Wang L Akiyoshi J Ma J Gai W Sidis Y Pitteloud N Kuro-O M Razzaque MS Mohammadi M 《Molecular and cellular biology》2012,32(10):1944-1954
It has been recently established that Klotho coreceptors associate with fibroblast growth factor (FGF) receptor tyrosine kinases (FGFRs) to enable signaling by endocrine-acting FGFs. However, the molecular interactions leading to FGF-FGFR-Klotho ternary complex formation remain incompletely understood. Here, we show that in contrast to αKlotho, βKlotho binds its cognate endocrine FGF ligand (FGF19 or FGF21) and FGFR independently through two distinct binding sites. FGF19 and FGF21 use their respective C-terminal tails to bind to a common binding site on βKlotho. Importantly, we also show that Klotho coreceptors engage a conserved hydrophobic groove in the immunoglobulin-like domain III (D3) of the "c" splice isoform of FGFR. Intriguingly, this hydrophobic groove is also used by ligands of the paracrine-acting FGF8 subfamily for receptor binding. Based on this binding site overlap, we conclude that while Klotho coreceptors enhance binding affinity of FGFR for endocrine FGFs, they actively suppress binding of FGF8 subfamily ligands to FGFR. 相似文献
999.
1000.
Sakaguchi K Matsuda T Kobayashi T Ohara J Hamaguchi R Abe E Nagano N Hayashi M Ueda M Honda D Okita Y Taoka Y Sugimoto S Okino N Ito M 《Applied and environmental microbiology》2012,78(9):3193-3202
A versatile transformation system for thraustochytrids, a promising producer for polyunsaturated fatty acids and fatty acid-derived fuels, was established. G418, hygromycin B, blasticidin, and zeocin inhibited the growth of thraustochytrids, indicating that multiple selectable marker genes could be used in the transformation system. A neomycin resistance gene (neo(r)), driven with an ubiquitin or an EF-1α promoter-terminator from Thraustochytrium aureum ATCC 34304, was introduced into representatives of two thraustochytrid genera, Aurantiochytrium and Thraustochytrium. The neo(r) marker was integrated into the chromosomal DNA by random recombination and then functionally translated into neo(r) mRNA. Additionally, we confirmed that another two genera, Parietichytrium and Schizochytrium, could be transformed by the same method. By this method, the enhanced green fluorescent protein was functionally expressed in thraustochytrids. Meanwhile, T. aureum ATCC 34304 could be transformed by two 18S ribosomal DNA-targeting vectors, designed to cause single- or double-crossover homologous recombination. Finally, the fatty acid Δ5 desaturase gene was disrupted by double-crossover homologous recombination in T. aureum ATCC 34304, resulting in an increase of dihomo-γ-linolenic acid (C(20:3n-6)) and eicosatetraenoic acid (C(20:4n-3)), substrates for Δ5 desaturase, and a decrease of arachidonic acid (C(20:4n-6)) and eicosapentaenoic acid (C(20:5n-3)), products for the enzyme. These results clearly indicate that a versatile transformation system which could be applicable to both multiple transgene expression and gene targeting was established for thraustochytrids. 相似文献