全文获取类型
收费全文 | 2764篇 |
免费 | 132篇 |
出版年
2023年 | 4篇 |
2022年 | 17篇 |
2021年 | 42篇 |
2020年 | 24篇 |
2019年 | 22篇 |
2018年 | 40篇 |
2017年 | 39篇 |
2016年 | 54篇 |
2015年 | 97篇 |
2014年 | 115篇 |
2013年 | 170篇 |
2012年 | 186篇 |
2011年 | 196篇 |
2010年 | 135篇 |
2009年 | 127篇 |
2008年 | 192篇 |
2007年 | 197篇 |
2006年 | 169篇 |
2005年 | 163篇 |
2004年 | 178篇 |
2003年 | 169篇 |
2002年 | 183篇 |
2001年 | 25篇 |
2000年 | 22篇 |
1999年 | 33篇 |
1998年 | 34篇 |
1997年 | 30篇 |
1996年 | 20篇 |
1995年 | 26篇 |
1994年 | 16篇 |
1993年 | 31篇 |
1992年 | 8篇 |
1991年 | 10篇 |
1990年 | 11篇 |
1989年 | 9篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 9篇 |
1982年 | 12篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1973年 | 4篇 |
排序方式: 共有2896条查询结果,搜索用时 171 毫秒
81.
Uemoto Y Suzuki S Terada N Ohno N Ohno S Yamanaka S Komada M 《The Journal of biological chemistry》2007,282(9):6548-6555
At axon initial segments and nodes of Ranvier in neurons, the spectrin membrane skeleton plays roles in physically stabilizing the plasma membrane integrity and in clustering voltage-gated sodium channels for proper conduction of the action potential. betaIV-Spectrin, an essential component of the membrane skeleton at these sites, has an N-terminal-truncated isoform, Sigma6, which is expressed at much higher levels than the full-length isoform Sigma1. To investigate the role of betaIV-spectrin Sigma6, we generated Sigma1-deficient mice with a normal level of Sigma6 expression (Sigma1(-/-) mice), and compared their phenotypes with those of previously generated mice lacking both Sigma1 and Sigma6(Sigma1Sigma6(-/-) mice). The gross neurological defects observed in Sigma1Sigma6(-/-) mice, such as hindleg contraction, were apparently ameliorated in Sigma1(-/-) mice. At cellular levels, Sigma1Sigma6(-/-) and Sigma1(-/-) neurons similarly exhibited waving and swelling of the plasma membrane at axon initial segments and nodes of Ranvier. By contrast, the levels of ankyrin G and voltage-gated sodium channels at these sites, which are significantly reduced in Sigma1Sigma6(-/-) mice, were substantially recovered in Sigma1(-/-) mice. We conclude that the truncated betaIV-spectrin isoform Sigma6 plays a specific role in clustering voltage-gated sodium channels, whereas it is dispensable for membrane stabilization at axon initial segments and nodes of Ranvier. 相似文献
82.
Hirotoshi Motoda Takayuki Sasaki Yoshio Kano Peter R Ryan Emmanuel Delhaize Hideaki Matsumoto Yoko Yamamoto 《Plant signaling & behavior》2007,2(6):467-472
The wheat ALMT1 gene encodes an aluminum (Al)-activated malate transport protein which confers Al-resistance. We investigated the membrane topology of this plasma-membrane localized protein with immunocytochemical techniques. Several green fluorescent protein (GFP)-fused and histidine (His)-tagged chimeras of ALMT1 were prepared based on a computer-predicted secondary structure and transiently expressed in cultured mammalian cells. Antibodies raised to polypeptide epitopes of ALMT1 were used in conjunction with the antibody to the His-tags to determine the topology of ALMT1. This study shows that the ALMT1 protein contains six transmembrane domains with the amino and carboxyl termini located on the extracellular side of the plasma membrane.Key Words: ALMT1, aluminum resistance, immunofluorescent staining, malate transporter, topology, Triticum aestivum 相似文献
83.
Regulation of ammonia homeostasis by the ammonium transporter AmtA in Dictyostelium discoideum
下载免费PDF全文
![点击此处可从《Eukaryotic cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yoshino R Morio T Yamada Y Kuwayama H Sameshima M Tanaka Y Sesaki H Iijima M 《Eukaryotic cell》2007,6(12):2419-2428
Ammonia has been shown to function as a morphogen at multiple steps during the development of the cellular slime mold Dictyostelium discoideum; however, it is largely unknown how intracellular ammonia levels are controlled. In the Dictyostelium genome, there are five genes that encode putative ammonium transporters: amtA, amtB, amtC, rhgA, and rhgB. Here, we show that AmtA regulates ammonia homeostasis during growth and development. We found that cells lacking amtA had increased levels of ammonia/ammonium, whereas their extracellular ammonia/ammonium levels were highly decreased. These results suggest that AmtA mediates the excretion of ammonium. In support of a role for AmtA in ammonia homeostasis, AmtA mRNA is expressed throughout the life cycle, and its expression level increases during development. Importantly, AmtA-mediated ammonia homeostasis is critical for many developmental processes. amtA(-) cells are more sensitive to NH(4)Cl than wild-type cells in inhibition of chemotaxis toward cyclic AMP and of formation of multicellular aggregates. Furthermore, even in the absence of exogenously added ammonia, we found that amtA(-) cells produced many small fruiting bodies and that the viability and germination of amtA(-) spores were dramatically compromised. Taken together, our data clearly demonstrate that AmtA regulates ammonia homeostasis and plays important roles in multiple developmental processes in Dictyostelium. 相似文献
84.
85.
Akihiro Hirata Yoko Miyamoto Akihisa Kaneko Hiroki Sakai Kyoko Yoshizaki Tokuma Yanai Takako Miyabe‐Nishiwaki Juri Suzuki 《Journal of medical primatology》2019,48(2):137-140
Primary neuroendocrine neoplasm of the liver is extremely rare in both humans and non‐human primates. The present report describes the clinical and pathological findings of an aged Japanese macaque (Macaca fuscata) with hepatic neuroendocrine carcinoma. To our knowledge, this is the first report of hepatic neuroendocrine neoplasm in macaques. 相似文献
86.
Yoko Nakagawa Naofumi Nakayama Hitoshi Goto Ikuhide Fujisawa Soda Chanthamath Kazutaka Shibatomi Seiji Iwasa 《Chirality》2019,31(1):52-61
Computational chemical analysis of Ru(II)‐Pheox–catalyzed highly enantioselective intramolecular cyclopropanation reactions was performed using density functional theory (DFT). In this study, cyclopropane ring–fused γ‐lactones, which are 5.8 kcal/mol more stable than the corresponding minor enantiomer, are obtained as the major product. The results of the calculations suggest that the enantioselectivity of the Ru(II)‐Pheox–catalyzed intramolecular cyclopropanation reaction is affected by the energy differences between the starting structures 5l and 5i . The reaction pathway was found to be a stepwise mechanism that proceeds through the formation of a metallacyclobutane intermediate. This is the first example of a computational chemical analysis of enantioselective control in an intramolecular carbene‐transfer reaction using C1‐symmetric catalysts. 相似文献
87.
Akihiro Kuno Yoshihisa Ikeda Shinya Ayabe Kanako Kato Kotaro Sakamoto Sayaka R. Suzuki Kento Morimoto Arata Wakimoto Natsuki Mikami Miyuki Ishida Natsumi Iki Yuko Hamada Megumi Takemura Yoko Daitoku Yoko Tanimoto Tra Thi Huong Dinh Kazuya Murata Michito Hamada Masafumi Muratani Atsushi Yoshiki Fumihiro Sugiyama Satoru Takahashi Seiya Mizuno 《PLoS biology》2022,20(1)
Genome editing can introduce designed mutations into a target genomic site. Recent research has revealed that it can also induce various unintended events such as structural variations, small indels, and substitutions at, and in some cases, away from the target site. These rearrangements may result in confounding phenotypes in biomedical research samples and cause a concern in clinical or agricultural applications. However, current genotyping methods do not allow a comprehensive analysis of diverse mutations for phasing and mosaic variant detection. Here, we developed a genotyping method with an on-target site analysis software named Determine Allele mutations and Judge Intended genotype by Nanopore sequencer (DAJIN) that can automatically identify and classify both intended and unintended diverse mutations, including point mutations, deletions, inversions, and cis double knock-in at single-nucleotide resolution. Our approach with DAJIN can handle approximately 100 samples under different editing conditions in a single run. With its high versatility, scalability, and convenience, DAJIN-assisted multiplex genotyping may become a new standard for validating genome editing outcomes.Genome editing can introduce designed mutations into a target genomic site, but also into unintended off-target sites. DAJIN, a novel nanopore sequencing data analysis tool, identifies and quantifies allele numbers and their mutation patterns, reporting consensus sequences and visualizing mutations in alleles at single-nucleotide resolution. 相似文献
88.
Yoko Ono Atsuko Noda Yasuhiro Zaima Narumi Jitsufuchi Seijo Eto Hiroshi Noda 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1996,677(2):339
In comparison with the hepatocytes obtained from intact rats and rats pretreated with phenobarbital or 3-methylchoranthrene, the amount of isonicotinic acid (INA) formed from isoniazid (INH) increased substantially after incubation at 37°C using the pretreated hepatocytes. This suggests an oxidative pathway for INA formation from INH, apart from hydrolysis. In order to explore the exact mechanism of INA formation in the hepatocytes, an HPLC assay for INA in the presence of INH and acetylisoniazid was developed. In this assay, INA was extracted after the preparation of an ion pair with tetra-n-butylammonium hydroxide, and analysed using an ODS column and a mobile phase consisting of 0.067 M potassium dihydrogenphosphate solution-methanol (96:4 v/v). The method is simple, accurate and especially suitable for INA determination after incubation of INH in isolated rat hepatocytes. 相似文献
89.
Introns are generally believed to evolve too rapidly and too erratically to be of much use in phylogenetic reconstructions.
Few phylogenetically informative intron sequences are available, however, to ascertain the validity of this supposition. In
the present study the supposition was tested on the example of the mammalian class II major histocompatibility complex (Mhc) genes of the DRB family. Since the Mhc genes evolve under balancing selection and are believed to recombine or rearrange frequently, the evolution of their introns
could be expected to be particularly rapid and subject to scrambling. Sequences of intron 4 and 5 DRB genes were obtained from polymerase chain reaction-amplified fragments of genomic DNA from representatives of six eutherian
orders—Primates, Scandentia, Chiroptera, Dermoptera, Lagomorpha, and Insectivora. Although short stretches of the introns
have indeed proved to be unalignable, the bulk of the intron sequences from all six orders, spanning >85 million years (my)
of evolution, could be aligned and used in a study of the tempo and mode of intron evolution. The analysis has revealed the
Mhc introns to evolve at a rate similar to that of other genes and of synonymous sites of non-Mhc genes. No evidence of homogenization or large-scale scrambling of the intron sequences could be found. The Mhc introns apparently evolve largely by point mutations and insertions/deletions. The phylogenetic signals contained in the
intron sequences could be used to identify Scandentia as the sister group of Primates, to support the existence of the Archonta
superorder, and to confirm the monophyly of the Chiroptera.
Received: 26 October 1998 / Accepted: 21 December 1998 相似文献
90.
Cytoplasmic dynein is a minus-end directed microtubule motor and plays important roles in the transport of various intracellular cargoes. Cytoplasmic dynein comprises two identical heavy chains and forms a dimer (double-headed dynein); the total molecular weight of the cytoplasmic dynein complex is about 1.5 million. The dynein motor domain is structurally very different from those of kinesin and myosin, and our understanding of the mechanisms of dynein energy transduction is limited mainly because of the difficulty in obtaining a sufficient quantity of purified and active cytoplasmic dynein. We purified cytoplasmic dynein, which was free from dynactin and other dynein-associated proteins. The purified cytoplasmic dynein was active in an in vitro motility assay. The controlled dialysis of the purified dynein against 4 M urea resulted in its complete dissociation into monomeric species (single-headed dynein). The separation of the dynein heads by the treatment was reversible. The MgATPase activities of the single-headed and reconstituted double-headed dynein were comparable to that of intact dynein. The double-headed dynein bundled microtubules in the absence of ATP; the single-headed dynein did not. The single-headed dynein produced in vitro microtubule-gliding motility at velocities very similar to those of double-headed dynein at various ATP concentrations. These results indicate that a single cytoplasmic dynein heavy chain is sufficient to produce robust microtubule motility. Application of the double- and single-headed dynein molecules in various assay systems will elucidate the mechanism of action of the cytoplasmic dynein. 相似文献