全文获取类型
收费全文 | 1192篇 |
免费 | 79篇 |
出版年
2022年 | 16篇 |
2021年 | 17篇 |
2020年 | 8篇 |
2019年 | 14篇 |
2018年 | 20篇 |
2017年 | 30篇 |
2016年 | 36篇 |
2015年 | 42篇 |
2014年 | 59篇 |
2013年 | 75篇 |
2012年 | 103篇 |
2011年 | 99篇 |
2010年 | 54篇 |
2009年 | 62篇 |
2008年 | 81篇 |
2007年 | 93篇 |
2006年 | 86篇 |
2005年 | 78篇 |
2004年 | 62篇 |
2003年 | 68篇 |
2002年 | 52篇 |
2001年 | 3篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 16篇 |
1997年 | 21篇 |
1996年 | 9篇 |
1995年 | 14篇 |
1994年 | 11篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有1271条查询结果,搜索用时 15 毫秒
181.
Shin K Horigome A Yamauchi K Takase M Yaeshima T Iwatsuki K 《Bioscience, biotechnology, and biochemistry》2008,72(7):1932-1935
The effect of lactoperoxidase (LPO) on dextran sulfate sodium-induced colitis was examined in mice. After 9 d of colitis induction, weight loss, colon shortening, and the histological score were significantly suppressed in mice orally administered LPO (62.5 mg/body/d) as compared to a group administered bovine serum albumin. These results suggest that LPO exhibits anti-inflammatory effects in the gastrointestinal tract. 相似文献
182.
Umehara K Nemoto K Kimijima K Matsushita A Terada E Monthakantirat O De-Eknamkul W Miyase T Warashina T Degawa M Noguchi H 《Phytochemistry》2008,69(2):546-552
From the heartwood of Dalbergia parviflora, five compounds, dalparvin A (1), B (2), C (3), dalparvinol C (4), and neokhriol A (5), along with 11 known compounds, kenusanone G (6), cajanin (7), sophorol (8), alpinetin (9), hesperetin (10), 3'-O-methylorobol, odoratin, (2R)(3R)-2,3-trans 7-hydroxy-5-methoxydihydroflavonol, (6aR, 11aR)-3,8-dihydroxy-9-methoxypterocarpan, (6aR, 11aR)- vesticarpan, and methyl-3,4-dihydroxy-2-methoxybenzoate were isolated and characterized. Isolates were evaluated for their cell proliferation stimulatory activity against MCF-7, T-47D, and BT20 human breast cancer cell lines. Along with 7-10, two compounds 2 and 3 stimulated not only MCF-7, but also T-47D human breast cancer cell proliferation. Compound 6 had activity only against MCF-7 cells, and the activity of 7 was more than equivalent to that of daidzein. On the other hand, none of the isolates had any significant effects on BT20 cell proliferation, and these results indicated that the stimulative activity of these compounds was not general to any cell proliferations. Furthermore, these compounds were tested in the estrogen-responsive transient luciferase reporter assay. 相似文献
183.
It has been established that a long DNA molecule exhibits a large discrete conformational change from a coiled state to a highly folded state in aqueous solution, depending on the presence of various condensing agents such as polyamines. In this study, T4 DNA labeled with fluorescent dyes was encapsulated in a cell-sized microdroplet covered with a phospholipid membrane to investigate the conformational behavior of a DNA molecule in such a confined space. Fluorescence microscopy showed that the presence of Mg2+ induced the adsorption of DNA onto the membrane inner-surface of a droplet composed of phosphatidylethanolamine, while no adsorption was observed onto a phosphatidylcholine membrane. Under the presence of spermine (tetravalent amine), DNA had a folded conformation in the bulk solution. However, when these molecules were encapsulated in the microdroplet, DNA adsorbed onto the membrane surface accompanied by unfolding of its structure into an extended coil conformation under high concentrations of Mg2+. In addition, DNA molecules trapped in large droplets tended not to be adsorbed on the membrane, i.e., no conformational transition occurred. A thermodynamic analysis suggests that the translational entropy loss of a DNA molecule that is accompanied by adsorption is a key factor in these phenomena under micrometer-scale confinement. 相似文献
184.
185.
Reiko Nakao Katsuya Hirasaka Jumpei Goto Kazumi Ishidoh Chiharu Yamada Ayako Ohno Yuushi Okumura Ikuya Nonaka Koji Yasutomo Kenneth M. Baldwin Eiki Kominami Akira Higashibata Keisuke Nagano Keiji Tanaka Natsuo Yasui Edward M. Mills Shin'ichi Takeda Takeshi Nikawa 《Molecular and cellular biology》2009,29(17):4798-4811
186.
The Senescence-accelerated Mouse (SAM): A Higher Oxidative Stress and Age-dependent Degenerative Diseases Model 总被引:1,自引:0,他引:1
Chiba Y Shimada A Kumagai N Yoshikawa K Ishii S Furukawa A Takei S Sakura M Kawamura N Hosokawa M 《Neurochemical research》2009,34(4):679-687
The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone)
and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated
senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes
similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial
dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function.
Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive
production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice.
These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop
clinical interventions.
Special issue article in honor of Dr. Akitane Mori. 相似文献
187.
Ayako Furukawa Takashi Nagata Akimasa Matsugami Yuichirou Habu Ryuichi Sugiyama Fumiaki Hayashi Naohiro Kobayashi Shigeyuki Yokoyama Hiroshi Takaku Masato Katahira 《The EMBO journal》2009,28(4):440-451
Human APOBEC3G exhibits anti‐human immunodeficiency virus‐1 (HIV‐1) activity by deaminating cytidines of the minus strand of HIV‐1. Here, we report a solution structure of the C‐terminal deaminase domain of wild‐type APOBEC3G. The interaction with DNA was examined. Many differences in the interaction were found between the wild type and recently studied mutant APOBEC3Gs. The position of the substrate cytidine, together with that of a DNA chain, in the complex, was deduced. Interestingly, the deamination reaction of APOBEC3G was successfully monitored using NMR signals in real time. Real‐time monitoring has revealed that the third cytidine of the d(CCCA) segment is deaminated at an early stage and that then the second one is deaminated at a late stage, the first one not being deaminated at all. This indicates that the deamination is carried out in a strict 3′ → 5′ order. Virus infectivity factor (Vif) of HIV‐1 counteracts the anti‐HIV‐1 activity of APOBEC3G. The structure of the N‐terminal domain of APOBEC3G, with which Vif interacts, was constructed with homology modelling. The structure implies the mechanism of species‐specific sensitivity of APOBEC3G to Vif action. 相似文献
188.
189.
Gadsby DC Takeuchi A Artigas P Reyes N 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2009,364(1514):229-238
In principle, an ion channel needs no more than a single gate, but a pump requires at least two gates that open and close alternately to allow ion access from only one side of the membrane at a time. In the Na+,K+-ATPase pump, this alternating gating effects outward transport of three Na+ ions and inward transport of two K+ ions, for each ATP hydrolysed, up to a hundred times per second, generating a measurable current if assayed in millions of pumps. Under these assay conditions, voltage jumps elicit brief charge movements, consistent with displacement of ions along the ion pathway while one gate is open but the other closed. Binding of the marine toxin, palytoxin, to the Na+,K+-ATPase uncouples the two gates, so that although each gate still responds to its physiological ligand they are no longer constrained to open and close alternately, and the Na+,K+-ATPase is transformed into a gated cation channel. Millions of Na+ or K+ ions per second flow through such an open pump-channel, permitting assay of single molecules and allowing unprecedented access to the ion transport pathway through the Na+,K+-ATPase. Use of variously charged small hydrophilic thiol-specific reagents to probe cysteine targets introduced throughout the pump's transmembrane segments allows mapping and characterization of the route traversed by transported ions. 相似文献
190.
Prolyl 4-Hydroxylation of ��-Fibrinogen: A NOVEL PROTEIN MODIFICATION REVEALED BY PLASMA PROTEOMICS*
Masaya Ono Junichi Matsubara Kazufumi Honda Tomohiro Sakuma Tomoyo Hashiguchi Hiroshi Nose Shoji Nakamori Takuji Okusaka Tomoo Kosuge Naohiro Sata Hideo Nagai Tatsuya Ioka Sachiko Tanaka Akihiko Tsuchida Tatsuya Aoki Masashi Shimahara Yohichi Yasunami Takao Itoi Fuminori Moriyasu Ayako Negishi Hideya Kuwabara Ayako Shoji Setsuo Hirohashi Tesshi Yamada 《The Journal of biological chemistry》2009,284(42):29041-29049
Plasma proteome analysis requires sufficient power to compare numerous samples and detect changes in protein modification, because the protein content of human samples varies significantly among individuals, and many plasma proteins undergo changes in the bloodstream. A label-free proteomics platform developed in our laboratory, termed “Two-Dimensional Image Converted Analysis of Liquid chromatography and mass spectrometry (2DICAL),” is capable of these tasks. Here, we describe successful detection of novel prolyl hydroxylation of α-fibrinogen using 2DICAL, based on comparison of plasma samples of 38 pancreatic cancer patients and 39 healthy subjects. Using a newly generated monoclonal antibody 11A5, we confirmed the increase in prolyl-hydroxylated α-fibrinogen plasma levels and identified prolyl 4-hydroxylase A1 as a key enzyme for the modification. Competitive enzyme-linked immunosorbent assay of 685 blood samples revealed dynamic changes in prolyl-hydroxylated α-fibrinogen plasma level depending on clinical status. Prolyl-hydroxylated α-fibrinogen is presumably controlled by multiple biological mechanisms, which remain to be clarified in future studies.For comprehensive analysis of plasma proteins, it is necessary to compare a sufficient number of blood samples to avoid simple interindividual heterogeneity, because the protein content of human samples varies significantly among individuals. Also, the provision of sufficient power is needed to detect protein modification because many plasma proteins undergo changes in the bloodstream (1). Even though the proteomic technologies have advanced (2, 3), there remains room for improvement. Different isotope labeling and identification-based methods have been developed for quantitative proteomics technologies (4–6), but the number of samples that can be compared by the current isotope-labeling methods is limited, and identification-based proteomics is unable to capture information regarding unknown modifications.A label-free proteomics platform developed in our laboratory, termed “Two-Dimensional Image Converted Analysis of Liquid chromatography and mass spectrometry (2DICAL)2 (7), simply compares the liquid chromatography and mass spectrometry (LC-MS) data and detects a protein modification by finding changes in the mass to charge ratio (m/z) and retention time (RT). Enhanced methods for accurate MS peak alignment across multiple LC runs have enabled the successful implementation of clinical studies requiring comparison of a large number of samples (8, 9). Using 2DICAL to analyze plasma samples of pancreatic cancer patients and healthy controls, novel prolyl hydroxylation of α-fibrinogen was successfully discovered.Fibrinogen and its modification has been investigated because of its clinical importance (10, 11). On the other hand, prolyl hydroxylation has attracted attention after the discovery of the hypoxia-inducible factor 1α (HIF1α) prolyl-hydroxylase and its role in switching of HIF1α functions (12). Prolyl hydroxylation in other proteins has been energetically sought, but only a few such proteins have been identified (13). Only one study has reported prolyl hydroxylation of fibrinogen at the β chain (14).Here, we report the detection of prolyl 4-hydroxylated α-fibrinogen by plasma proteome analysis, a protein modification that dynamically changes in plasma depending on the clinical status and is a candidate plasma biomarker. 相似文献