全文获取类型
收费全文 | 3285篇 |
免费 | 185篇 |
国内免费 | 2篇 |
专业分类
3472篇 |
出版年
2022年 | 20篇 |
2021年 | 42篇 |
2020年 | 22篇 |
2019年 | 42篇 |
2018年 | 40篇 |
2017年 | 50篇 |
2016年 | 73篇 |
2015年 | 114篇 |
2014年 | 124篇 |
2013年 | 204篇 |
2012年 | 223篇 |
2011年 | 205篇 |
2010年 | 143篇 |
2009年 | 152篇 |
2008年 | 198篇 |
2007年 | 206篇 |
2006年 | 186篇 |
2005年 | 193篇 |
2004年 | 175篇 |
2003年 | 169篇 |
2002年 | 170篇 |
2001年 | 38篇 |
2000年 | 30篇 |
1999年 | 51篇 |
1998年 | 34篇 |
1997年 | 36篇 |
1996年 | 31篇 |
1995年 | 22篇 |
1994年 | 17篇 |
1993年 | 32篇 |
1992年 | 43篇 |
1991年 | 43篇 |
1990年 | 33篇 |
1989年 | 40篇 |
1988年 | 27篇 |
1987年 | 18篇 |
1986年 | 25篇 |
1985年 | 21篇 |
1984年 | 25篇 |
1983年 | 22篇 |
1982年 | 27篇 |
1981年 | 15篇 |
1980年 | 7篇 |
1979年 | 11篇 |
1978年 | 10篇 |
1975年 | 6篇 |
1974年 | 15篇 |
1973年 | 5篇 |
1972年 | 5篇 |
1967年 | 4篇 |
排序方式: 共有3472条查询结果,搜索用时 10 毫秒
61.
Masaki Wakasugi Hiroaki Gouda Tomoyasu Hirose Akihiro Sugawara Tsuyoshi Yamamoto Kazuro Shiomi Toshiaki Sunazuka Satoshi Ōmura Shuichi Hirono 《Bioorganic & medicinal chemistry》2013,21(11):3214-3220
Human acidic mammalian chitinase (hAMCase) was recently shown to be involved in the development of asthma, suggesting a possible application for hAMCase inhibitors as novel therapeutic agents for asthma. We therefore initiated drug discovery research into hAMCase using a combination of in silico methodologies and a hAMCase assay system. We first selected 23 candidate hAMCase inhibitors from a database of four million compounds using a multistep screening system combining Tripos Topomer Search technology, a docking calculation and two-dimensional molecular similarity analysis. We then measured hAMCase inhibitory activity of the selected compounds and identified seven compounds with IC50 values ?100 μM. A model describing the binding modes of these hit compounds to hAMCase was constructed, and we discuss the structure–activity relationships of the compounds we identified, suggested by the model and the actual inhibitory activities of the compounds. 相似文献
62.
63.
Amanita caesareoides is a sister species of Amanita caesarea, also known as Caesar’s mushroom and one of the most desirable edible mycorrhizal mushrooms. However, cultivation of Caesar’s mushrooms has not yet been successful due to the difficulties involved in establishing pure cultures. In this study, we established pure cultures of four Asian Caesar’s mushroom species, i.e., A. caesareoides, Amanita javanica, Amanita esculenta, and Amanita similis, which were identified by sequence analysis of their rDNA internal transcribed spacer (ITS) region. Five selected isolates in A. caesareoides, A. javanica, and A. esculenta were tested for ectomycorrhizal syntheses with axenic Pinus densiflora seedlings in vitro. Ectomycorrhizal tips of each fungal isolate tested were observed on pine lateral roots within 5 months of inoculation. Seventeen pine seedlings that formed ectomycorrhizas in vitro with these three Amanita species were acclimatized under non-sterile conditions. Seven months following acclimatization, ectomycorrhizal colonization by A. caesareoides was observed on newly grown root tips, which was confirmed by polymerase chain reaction restriction fragment length polymorphism analysis of the fungal rDNA ITS region. Two other Amanita species also survived during ectomycorrhizal acclimatization. These results suggest that the cultivation of A. caesareoides and its relatives can be attempted through mycorrhizal synthesis using P. densiflora as a host. This is the first report of in vitro mycorrhization of Asian Caesar’s mushrooms and their acclimatization under non-sterile conditions. 相似文献
64.
Masaki Nakahara Nobuaki Kitahara Kiyoshi Hamano Mamoru Arat Hiroshi Okazaki 《Bioscience, biotechnology, and biochemistry》2013,77(9):1821-1826
Studies on lipopolysaccharide (LPS) from the cells of Proteus mirabilis RMS-203 were focused upon reduction of lethal toxicity and of pyrogenicity by biological and chemical modification. A heptoseless mutant, strain N-434, was isolated by the use of phage resistancy as a tool. LPS from that heptoseless mutant was completely deficient in neutral sugars and mainly composed of 2-keto-deoxy-octonic acid (KDO), glucosamine and fatty acids. It revealed almost the same antitumor activity as LPS of the wild type but it was less toxic and less pyrogenic.Hydroxylaminolysis and reduction with LiAlH4 resulted in removal of fatty acids from LPS accompanied with decrease in lethal toxicity and antitumor acitivity but not in pyrogenicity.Lipid A fractions showed almost the same antitumor activity as intact LPS but less lethality and less pyrogenicity. 相似文献
65.
Mamoru Arai Masaki Nakahara v Hamano Hiroshi Okazaki 《Bioscience, biotechnology, and biochemistry》2013,77(9):1813-1819
Systematic isolation of the cell constituents of Proteus mirabilis RMS–203 was performed to find out localization of antitumor principle only in the lipopolysaccharide (LPS) layer of the cell wall fraction.LPS with strong antitumor activity was extracted from P. mirabilis RMS–203 by phenol-water method followed by purification on DEAE-Sephadex A–50 column chromatography.The main components of purified LPS were galactose, hexosamine, 2-keto-deoxy-octonic acid (KDO), myristic acid, β-hydroxymyristic acid and α,ε-diaminopimelic acid.The minimal effective dose of LPS against Ehrlich solid carcinoma in mice was 0.1~1.0 μg/mouse. LD50 in mice and pyrogenicity in rabbits were 28 mg/kg and 10?3–10?5 μg/rabbit, respectively. 相似文献
66.
Reducing Molecular Flexibility by Cyclization for Elucidation of Absolute Configuration by CD Calculations: Daurichromenic Acid 下载免费PDF全文
Circular dichroism (CD) calculations of flexible natural products have been difficult because of the large number of low‐energy conformers and ambiguous Boltzmann distributions. In this article, through electronic (ECD) and vibrational (VCD) studies on a natural product, (+)‐daurichromenic acid, we demonstrate that derivatization of a flexible molecule can dramatically reduce its flexibility. This work also shows the usefulness of derivatization for diminishing computational expenses required for optimization and CD calculations, and for increasing the reliability of the assignment of absolute configuration. Chirality 28:453–459, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
67.
Masaki Kikugawa Hiroyasu Tsutsuki Tomoaki Ida Hidemitsu Nakajima Hideshi Ihara 《Bioscience, biotechnology, and biochemistry》2016,80(3):547-553
Ferulic acid (FA) has been reported to exhibit protective effects against amyloid-β (Aβ)-induced neurodegeneration in vitro and in vivo. Recently, we developed two water-soluble FA derivatives: 1-feruloyl glycerol and 1-feruloyl diglycerol. In this study, we examined the neuroprotective effects of these water-soluble FA derivatives on Aβ-induced neurodegeneration both in vitro and in vivo. FA and water-soluble FA derivatives inhibited Aβ aggregation and destabilized pre-aggregated Aβ to a similar extent. Furthermore, water-soluble FA derivatives, as well as FA, inhibited Aβ-induced neuronal cell death in cultured neuronal cells. In in vivo experiments, oral administration of water-soluble FA derivatives to mice improved Aβ-induced dysmnesia assessed by contextual fear conditioning test and protected hippocampal neurons against Aβ-induced neurotoxicity. This study provides useful evidence suggesting that water-soluble FA derivatives are expected to be effective neuroprotective agents. 相似文献
68.
Chieko Hosaka Makoto Kunisada Michiyo Koyanagi‐Aoi Taro Masaki Chihiro Takemori Mariko Taniguchi‐Ikeda Takashi Aoi Chikako Nishigori 《Pigment cell & melanoma research》2019,32(5):623-633
Induced pluripotent stem cell (iPSC) technology offers a novel approach for conversion of human primary fibroblasts into melanocytes. During attempts to explore various protocols for differentiation of iPSCs into melanocytes, we found a distinct and self‐renewing cell lineage that could differentiate into melanocytes, named as melanocyte precursor cells (MPCs). The MPCs exhibited a morphology distinctive from that of melanocytes, in lacking either the melanosomal structure or the melanocyte‐specific marker genes MITF, TYR, and SOX10. In addition, gene expression studies in the MPCs showed high‐level expression of WNT5A, ROR2, which are non‐canonical WNT pathway markers, and its related receptor TGFβR2. In contrast, MPC differentiation into melanocytes was achieved by activating the canonical WNT pathway using the GSK3β inhibitor. Our data demonstrated the distinct characteristic of MPCs' ability to differentiate into melanocytes, and the underlying mechanism of interfacing between canonical WNT signaling pathway and non‐canonical WNT signaling pathway. 相似文献
69.
70.
Phosphorylation of types III and IV intermediate filaments (IFs) is known to regulate their organization and function. Phosphorylation of the amino-terminal head domain sites on types III and IV IF proteins plays a key role in the assembly/disassembly of IF subunits into 10 nm filaments, and influences the phosphorylation of sites on the carboxyl-terminal tail domain. These phosphorylation events are largely under the control of second messenger-dependent protein kinases and provide the cells a mechanism to reorganize the IFs in response to the changes in second messenger levels. In mitotic cells, Cdk1, Rho kinase, PAK1 and Aurora-B kinase are believed to regulate vimentin and glial fibrillary acidic protein phosphorylation in a spatio-temporal manner. In neurons, the carboxyl-terminal tail domains of the NF-M and NF-H subunits of heteropolymeric neurofilaments (NFs) are highly phosphorylated by proline-directed protein kinases. The phosphorylation of carboxyl-terminal tail domains of NFs has been suspected to play roles in forming cross-bridges between NFs and microtubules, slowing axonal transport and promoting their integration into cytoskeleton lattice and, in doing so, to control axonal caliber and stabilize the axon. The role of IF phosphorylation in disease pathobiology is discussed. 相似文献