全文获取类型
收费全文 | 2411篇 |
免费 | 139篇 |
出版年
2022年 | 7篇 |
2021年 | 23篇 |
2020年 | 11篇 |
2019年 | 19篇 |
2018年 | 25篇 |
2017年 | 28篇 |
2016年 | 32篇 |
2015年 | 63篇 |
2014年 | 71篇 |
2013年 | 146篇 |
2012年 | 134篇 |
2011年 | 158篇 |
2010年 | 104篇 |
2009年 | 88篇 |
2008年 | 150篇 |
2007年 | 138篇 |
2006年 | 134篇 |
2005年 | 120篇 |
2004年 | 159篇 |
2003年 | 145篇 |
2002年 | 134篇 |
2001年 | 49篇 |
2000年 | 39篇 |
1999年 | 50篇 |
1998年 | 29篇 |
1997年 | 34篇 |
1996年 | 36篇 |
1995年 | 42篇 |
1994年 | 19篇 |
1993年 | 24篇 |
1992年 | 36篇 |
1991年 | 37篇 |
1990年 | 30篇 |
1989年 | 20篇 |
1988年 | 28篇 |
1987年 | 18篇 |
1986年 | 12篇 |
1985年 | 17篇 |
1984年 | 16篇 |
1983年 | 18篇 |
1982年 | 14篇 |
1981年 | 9篇 |
1980年 | 21篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 11篇 |
1976年 | 9篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1972年 | 3篇 |
排序方式: 共有2550条查询结果,搜索用时 234 毫秒
81.
Kateina Adamusov Solmaz Khosravi Satoru Fujimoto Andreas Houben Sachihiro Matsunaga Jií Fajkus Miloslava Fojtov 《The Plant journal : for cell and molecular biology》2020,102(4):678-687
Telomeres, nucleoprotein structures at the ends of linear eukaryotic chromosomes, are crucial for the maintenance of genome integrity. In most plants, telomeres consist of conserved tandem repeat units comprising the TTTAGGG motif. Recently, non‐canonical telomeres were described in several plants and plant taxons, including the carnivorous plant Genlisea hispidula (TTCAGG/TTTCAGG), the genus Cestrum (Solanaceae; TTTTTTAGGG), and plants from the Asparagales order with either a vertebrate‐type telomere repeat TTAGGG or Allium genus‐specific CTCGGTTATGGG repeat. We analyzed epigenetic modifications of telomeric histones in plants with canonical and non‐canonical telomeres, and further in telomeric chromatin captured from leaves of Nicotiana benthamiana transiently transformed by telomere CRISPR‐dCas9‐eGFP, and of Arabidopsis thaliana stably transformed with TALE_telo C‐3×GFP. Two combinatorial patterns of telomeric histone modifications were identified: (i) an Arabidopsis‐like pattern (A. thaliana, G. hispidula, Genlisea nigrocaulis, Allium cepa, Narcissus pseudonarcissus, Petunia hybrida, Solanum tuberosum, Solanum lycopersicum) with telomeric histones decorated predominantly by H3K9me2; (ii) a tobacco‐like pattern (Nicotiana tabacum, N. benthamiana, C. elegans) with a strong H3K27me3 signal. Our data suggest that epigenetic modifications of plant telomere‐associated histones are related neither to the sequence of the telomere motif nor to the lengths of the telomeres. Nor the phylogenetic position of the species plays the role; representatives of the Solanaceae family are included in both groups. As both patterns of histone marks are compatible with fully functional telomeres in respective plants, we conclude that the described specific differences in histone marks are not critical for telomere functions. 相似文献
82.
83.
84.
Takahashi Yumiko Sarkar Juli Yamada Jumpei Matsunaga Yutaka Nonaka Yudai Banjo Mai Sakaguchi Ryo Shinya Terunaga Hatta Hideo 《Journal of physiology and biochemistry》2021,77(3):469-480
Journal of Physiology and Biochemistry - To identify factors that influence post-exercise muscle glycogen repletion, we compared the glycogen recovery after level running with downhill running, an... 相似文献
85.
Kenta Shirasawa Hiroyuki Fukuoka Hiroshi Matsunaga Yuhko Kobayashi Issei Kobayashi Hideki Hirakawa Sachiko Isobe Satoshi Tabata 《DNA research》2013,20(6):593-603
With the aim of understanding relationship between genetic and phenotypic variations in cultivated tomato, single nucleotide polymorphism (SNP) markers covering the whole genome of cultivated tomato were developed and genome-wide association studies (GWAS) were performed. The whole genomes of six tomato lines were sequenced with the ABI-5500xl SOLiD sequencer. Sequence reads covering ∼13.7× of the genome for each line were obtained, and mapped onto tomato reference genomes (SL2.40) to detect ∼1.5 million SNP candidates. Of the identified SNPs, 1.5% were considered to confer gene functions. In the subsequent Illumina GoldenGate assay for 1536 SNPs, 1293 SNPs were successfully genotyped, and 1248 showed polymorphisms among 663 tomato accessions. The whole-genome linkage disequilibrium (LD) analysis detected highly biased LD decays between euchromatic (58 kb) and heterochromatic regions (13.8 Mb). Subsequent GWAS identified SNPs that were significantly associated with agronomical traits, with SNP loci located near genes that were previously reported as candidates for these traits. This study demonstrates that attractive loci can be identified by performing GWAS with a large number of SNPs obtained from re-sequencing analysis. 相似文献
86.
PrPsc, the pathogenic isoform of PrPc, can convert PrPc into PrPsc through direct interactions. PrPc oligomerization is a required processing step before PrPsc formation, and soluble oligomers appear to be the toxic species in amyloid-related disorders. In the current study, direct interactions between vitamin D2 and human recombinant PrPc (90–231) were observed by Biacore assay, and 3F4 antibody, specific for amino acid fragment 109–112 of PrPc, inhibited this interaction. An ELISA study using3F4 antibody showed that PrPc (101–130), corresponding sequence to human PrP, was affected by vitamin D2, supporting the results of Biacore studies and suggesting that the PrPc sequence around the 3F4 epitope was responsible for the interaction with vitamin D2. Furthermore, the effects of vitamin D2 on disruption of PrPc (90–231) oligomerization were elucidated by dot blot analysis and differential protease k susceptibilities. While many chemical compounds have been proposed as potential therapeutic agents for the treatment of scrapie, most of these are toxic. However, given the safety and blood brain barrier permeability of vitamin D2, we propose that vitamin D2 may be a suitable agent to target PrPc in the brain and therefore is a potential therapeutic candidate for prion disease. 相似文献
87.
Kenichi Tanaka Masaaki Nakayama Makoto Kanno Hiroshi Kimura Kimio Watanabe Yoshihiro Tani Yuki Kusano Hodaka Suzuki Yoshimitsu Hayashi Koichi Asahi Keiji Sato Toshio Miyata Tsuyoshi Watanabe 《PloS one》2013,8(12)
Background
Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD).Methods
Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis.Results
Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004).Conclusions
Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD. 相似文献88.
Yoriko Yukitatsu Masaki Hata Koji Yamanegi Naoko Yamada Hideki Ohyama Keiji Nakasho Yusuke Kojima Hideki Oka Kenzo Tsuzuki Masafumi Sakagami Nobuyuki Terada 《Cell and tissue research》2013,352(3):647-657
VE-cadherin and claudin-5 are major components of adherens and tight junctions of vascular endothelial cells and a decrease in their expression and an increase in the tyrosine-phosphorylation of VE-cadherin are associated with an increase in endothelial paracellular permeability. To clarify the mechanism underlying the development of edema in nasal polyps, we studied these molecules in polyp microvessels. Normal inferior turbinate mucosal tissues and nasal polyps from patients treated with or without glucocorticoid were stained for VE-cadherin or claudin-5 and CD31 by a double-immunofluorescence method and the immunofluorescence intensities were graded 1–3 with increasing intensity. To correct for differences in fluorescence intensity attributable to a different endothelial area being exposed in a section or to the thickness of a section, the relative immunofluorescence intensity was estimated by dividing the grade of VE-cadherin or claudin-5 by that of CD31 in each microvessel. Tyrosine-phosphorylation of VE-cadherin was examined by Western blot analysis. The relative intensities of VE-cadherin and claudin-5 in the CD31-positive microvessels significantly decreased in the following order; inferior turbinate mucosa, treated polyps and untreated polyps. The ratio of tyrosine-phosphorylated VE-cadherin to VE-cadherin was significantly higher in untreated polyps than in the inferior turbinate mucosa and treated polyps, between which no significant difference in the ratio was seen. Thus, in nasal polyps, the barrier function of endothelial adherens and tight junctions is weakened, although glucocorticoid treatment improves this weakened barrier function. 相似文献
89.
Yoshiteru Sasaki Soichi Sano Masaki Nakahara Shigeo Murata Kohei Kometani Yuichi Aiba Shinji Sakamoto Yoshihiro Watanabe Keiji Tanaka Tomohiro Kurosaki Kazuhiro Iwai 《The EMBO journal》2013,32(18):2463-2476
The linear ubiquitin chain assembly complex (LUBAC) plays a crucial role in activating the canonical NF‐κB pathway, which is important for B‐cell development and function. Here, we describe a mouse model (B‐HOIPΔlinear) in which the linear polyubiquitination activity of LUBAC is specifically ablated in B cells. Canonical NF‐κB and ERK activation, mediated by the tumour necrosis factor (TNF) receptor superfamily receptors CD40 and TACI, was impaired in B cells from B‐HOIPΔlinear mice due to defective activation of the IKK complex; however, B‐cell receptor (BCR)‐mediated activation of the NF‐κB and ERK pathways was unaffected. B‐HOIPΔlinear mice show impaired B1‐cell development and defective antibody responses to thymus‐dependent and thymus‐independent II antigens. Taken together, these data suggest that LUBAC‐mediated linear polyubiquitination is essential for B‐cell development and activation, possibly via canonical NF‐κB and ERK activation induced by the TNF receptor superfamily, but not by the BCR. 相似文献
90.
Keiji Nagaya Yoshihiko Matsui Hironobu Ohira Akira Yuasa Hiroyuki Yamamoto Kousaku Ohkawa 《Biofouling》2013,29(4):263-274
The attachment strength of the freshwater mussel Limnoperna fortunei against water flow was studied. Newton's expression successfully described the hydrodynamic drag force acting on the mussel with a drag coefficient value of 1.03. The drag‐resistant force (defined as hydrodynamic drag force at mussel detachment) was smaller than the detachment force measured using a tensile load test. A fairly good correlation was obtained between the drag‐resistant force and the number of secreted threads. The drag‐resistant force divided by the number of threads increased with shell size, suggesting that byssal thread strength increased with mussel growth. For the mussel specimens obtained from a water transmission pipe, thread width increased with shell size. However, thread width was not dependent on current velocity. There was no correlation between the number of secreted threads and shell length, which indicated that the number of secreted threads did not change with mussel size. Therefore, the water velocity needed to detach mussels increases with shell size of the mussel when the number of secreted threads is constant. The increases in the water velocity to detach mussels with larger shells suggests that the mussel becomes more resistant to water flow as it grows. It is estimated that a flow velocity of around lms‐1 is critical for attachment/detachment of a juvenile mussel with a shell length of a few millimeters and one hundred byssal threads. 相似文献