全文获取类型
收费全文 | 659篇 |
免费 | 28篇 |
出版年
2022年 | 4篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 6篇 |
2014年 | 19篇 |
2013年 | 16篇 |
2012年 | 34篇 |
2011年 | 48篇 |
2010年 | 34篇 |
2009年 | 24篇 |
2008年 | 43篇 |
2007年 | 48篇 |
2006年 | 46篇 |
2005年 | 41篇 |
2004年 | 56篇 |
2003年 | 33篇 |
2002年 | 35篇 |
2001年 | 19篇 |
2000年 | 22篇 |
1999年 | 13篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 2篇 |
1990年 | 9篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有687条查询结果,搜索用时 171 毫秒
51.
Summary Visual membranes of the crayfish eye either belong to the small, distally placed rhabdomere of retinula cell R8 or are part of the much more voluminous proximal rhabdom, made up of rhabdomeres belonging to cells R1–R7. Under various conditions of environmental stress (e.g., prolonged darkness, elevated temperature, bright light with and without a concomitant rise in temperature, flickering lights) the visual membranes of R8 prove far more resistant to structural damage than those of R1–R7. Membrane damage is known to occur when dormant lipoxygenases become activated, for example through heat. Since R8 is the only type of visual cell in the crayfish retina that does not contain grains of screening pigment, the view that screening-pigment granules could aggravate or even trigger membrane damage in times of stress is strengthened. Functionally, R8's strong resistance to physical damage when exposed to flickering lights points to a role of the distal rhabdom in the movement detection system of the crayfish eye. 相似文献
52.
53.
Nogawa M Takahashi H Kashiwagi A Ohshima K Okada H Morikawa Y 《Applied and environmental microbiology》1998,64(3):890-895
Chitosan-degrading activities induced by glucosamine (GlcN) or N-acetylglucosamine (GlcNAc) were found in a culture filtrate of Trichoderma reesei PC-3-7. One of the chitosan-degrading enzymes was purified to homogeneity by precipitation with ammonium sulfate followed by anion-exchange and hydrophobic-interaction chromatographies. The enzyme was monomeric, and its molecular mass was 93 kDa. The optimum pH and temperature of the enzyme were 4.0 and 50 degrees C, respectively. The activity was stable in the pH range 6.0 to 9.0 and at a temperature below 50 degrees C. Reaction product analysis from the viscosimetric assay and thin-layer chromatography and H nuclear magnetic resonance spectroscopy clearly indicated that the enzyme was an exo-type chitosanase, exo-beta-d-glucosaminidase, that releases GlcN from the nonreducing end of the chitosan chain. H nuclear magnetic resonance spectroscopy also showed that the exo-beta-d-glucosaminidase produced a beta-form of GlcN, demonstrating that the enzyme is a retaining glycanase. Time-dependent liberation of the reducing sugar from partially acetylated chitosan with exo-beta-d-glucosaminidase and the partially purified exo-beta-d-N-acetylglucosaminidase from T. reesei PC-3-7 suggested that the exo-beta-d-glucosaminidase cleaves the glycosidic link of either GlcN-beta(1-->4)-GlcN or GlcN-beta(1-->4)-GlcNAc. 相似文献
54.
Osamu Nureki Patrick O’Donoghue Nobuhisa Watanabe Atsuhiko Ohmori Hiroyuki Oshikane Yuhei Araiso Kelly Sheppard Dieter S?ll Ryuichiro Ishitani 《Nucleic acids research》2010,38(20):7286-7297
The molecular basis of the genetic code relies on the specific ligation of amino acids to their cognate tRNA molecules. However, two pathways exist for the formation of Gln-tRNAGln. The evolutionarily older indirect route utilizes a non-discriminating glutamyl-tRNA synthetase (ND-GluRS) that can form both Glu-tRNAGlu and Glu-tRNAGln. The Glu-tRNAGln is then converted to Gln-tRNAGln by an amidotransferase. Since the well-characterized bacterial ND-GluRS enzymes recognize tRNAGlu and tRNAGln with an unrelated α-helical cage domain in contrast to the β-barrel anticodon-binding domain in archaeal and eukaryotic GluRSs, the mode of tRNAGlu/tRNAGln discrimination in archaea and eukaryotes was unknown. Here, we present the crystal structure of the Methanothermobacter thermautotrophicus ND-GluRS, which is the evolutionary predecessor of both the glutaminyl-tRNA synthetase (GlnRS) and the eukaryotic discriminating GluRS. Comparison with the previously solved structure of the Escherichia coli GlnRS-tRNAGln complex reveals the structural determinants responsible for specific tRNAGln recognition by GlnRS compared to promiscuous recognition of both tRNAs by the ND-GluRS. The structure also shows the amino acid recognition pocket of GluRS is more variable than that found in GlnRS. Phylogenetic analysis is used to reconstruct the key events in the evolution from indirect to direct genetic encoding of glutamine. 相似文献
55.
E. E. Syroechkovski P. S. Tomkovich M. Kashiwagi I. A. Taldenkov V. A. Buzin E. G. Lappo C. Zöckler 《Biology Bulletin》2010,37(9):941-951
The spoon-billed sandpiper is endemic of the northern Russian Far East and one of the rarest wader species in the world. During
a field survey (summer 2002) of the coast of Kolyuchinskaya Bay and in lagoons located to the east, it was discovered that
the species breeding population has declined by 3–5 times since the 1970s and amounted to only 42–50 breeding pairs. The reasons
for this decline are uncertain. They seem to occur outside the breeding grounds, on staging or wintering areas in South Eastern
Asia. The breeding productivity of the spoon-billed sandpiper is relatively low, but it did not decrease in recent decades.
The breeding success in 2002 was higher than in the 1980s; however, it was still about half of the minimum level necessary
to keep the local breeding population stable. Annual survival of the spoon-billed sandpiper is about 5–15% lower than in several
other small Calidridinae waders. An increased mortality rather than decreased productivity appears to be responsible for the
general decline of the spoon-billed sandpiper population. In the early 2000s, its total world population was estimated at
350–500 breeding pairs. The estimate of the spoonbilled sandpiper population obtained by Flint and Kondratyev (1977) is likely
an overestimate. 相似文献
56.
Nobuhisa Ozaki Arigala Uma Ravi Sankar Mitsuji Yamashita Takashi Aoki Yasutaka Tanaka Motohiko Kimura Mitsuo Toda Michio Fujie Yasuo Takehara Harumi Sakahara 《Bioorganic & medicinal chemistry letters》2010,20(3):932-934
A new type of dendritic molecules Gd-DTPA-XDA-D1-Glc(OH), which work as a functionalized ligand coordinating gadolinium(III) ion at the center of their frameworks with two glucose moieties on the molecular surfaces, were readily synthesized with high yield. The structures were established by IR, 1H, 13C NMR, and mass spectral studies. Its bio-distribution patterns were evaluated on rats. 相似文献
57.
Manabu Yamada Mitsuji Yamashita Takuya Suyama Junko Yamashita Kazuhide Asai Taishi Niimi Nobuhisa Ozaki Michio Fujie Kasthuraiah Maddali Satoki Nakamura Kazunori Ohnishi 《Bioorganic & medicinal chemistry letters》2010,20(19):5943-5946
4-Bromo-3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (3c) was first synthesized from 3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (2c) by a bromo-radical substitution reaction occurred at C-4 position by N-bromosuccinimide and 2,2′-azobisisobutyronitrile. The novel phospha sugar analogue 3c exerted high anti-proliferative effect on U937 cells evaluated by MTT in vitro methods and was much more efficient than that of Gleevec®, which is known as a molecule targeting chemotherapeutical agent. The substitution of 2-phospholenes at C-3 and C-4 position with methyl groups as well as 4-bromo substituent suggests a good anti-proliferative effect. 相似文献
58.
Nobuhisa Aoyagi Akira Kuzuya Jun Kawamata Ayae Kinoshita 《Biochemical and biophysical research communications》2010,391(2):1240-25316
γ-Secretase is an enzymatic complex, composed of presenilin 1 (PS1), nicastrin, pen-2, and aph-1, and is responsible for the intramembranous cleavage of various type-I membrane proteins. The level of each component is tightly regulated in a cell via proteasomal degradation. On the other hand, it has previously been reported that PS1/γ-secretase is involved in the activation of phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway. PI3K is inhibited in Alzheimer’s disease (AD) brain, whereas the effects of PI3K inhibition on the metabolism of PS1/γ-secretase have not been elucidated. Here, we demonstrate that the treatment of neurons with PI3K inhibitors leads to increased levels of PS1/γ-secretase components through an inhibitory effect on their degradation. Moreover, PI3K inhibition accelerated ubiquitination of PS1. We further show the evidence that the PS1 ubiquitination after PI3K inhibition is represented by the multiple mono-ubiquitination, instead of poly-ubiquitination. Accordingly, treatment of cells with PI3K inhibitor led to a differential intracellular redistribution of PS1 from the one observed after the proteasomal inhibition. These results suggest that PI3K inhibition may trigger the multiple mono-ubiquitination of PS1, which precludes the degradation of PS1/γ-secretase through the proteasomal pathway. Since PS1/γ-secretase is deeply involved in the production of Aβ protein, a deeper knowledge into its metabolism could contribute to a better elucidation of AD pathogenesis. 相似文献
59.
Gendron C Kashiwagi M Lim NH Enghild JJ Thøgersen IB Hughes C Caterson B Nagase H 《The Journal of biological chemistry》2007,282(25):18294-18306
Aggrecanases have been characterized as proteinases that cleave the Glu373-Ala374 bond of the aggrecan core protein, and they are multidomain metalloproteinases belonging to the ADAMTS (adamalysin with thrombospondin type 1 motifs) family. The first aggrecanases discovered were ADAMTS-4 (aggrecanase 1) and ADAMTS-5 (aggrecanase 2). They contain a zinc catalytic domain followed by non-catalytic ancillary domains, including a disintegrin domain, a thrombospondin domain, a cysteine-rich domain, and a spacer domain. In the case of ADAMTS-5, a second thrombospondin domain follows the spacer domain. We previously reported that the non-catalytic domains of ADAMTS-4 influence both its extracellular matrix interaction and proteolytic abilities. Here we report the effects of these domains of ADAMTS-5 on the extracellular matrix interaction and proteolytic activities and compare them with those of ADAMTS-4. Although the spacer domain was critical for ADAMTS-4 localization in the matrix, the cysteine-rich domain influenced ADAMTS-5 localization. Similar to previous reports of other ADAMTS family members, very little proteolytic activity was detected with the ADAMTS-5 catalytic domain alone. The sequential inclusion of each carboxyl-terminal domain enhanced its activity against aggrecan, carboxymethylated transferrin, fibromodulin, decorin, biglycan, and fibronectin. Both ADAMTS-4 and -5 had a broad optimal activity at pH 7.0-9.5. Aggrecanolytic activities were sensitive to the NaCl concentration, but activities on non-aggrecan substrates, e.g. carboxymethylated transferrin, were not affected. Although ADAMTS-4 and ADAMTS-5 had similar general proteolytic activities, the aggrecanase activity of ADAMTS-5 was at least 1,000-fold greater than that of ADAMTS-4 under physiological conditions. Our studies suggest that ADAMTS-5 is a major aggrecanase in cartilage metabolism and pathology. 相似文献
60.
Inamori Y Ota M Inoko H Okada E Nishizaki R Shiota T Mok J Oka A Ohno S Mizuki N 《Human genetics》2007,122(2):151-157
The collagen type Ι alpha Ι (COL1A1) gene encodes the extracellular matrix component, collagen, and resides in candidate MYP5
for high myopia on the chromosome 17q22–q23.3. This locus has recently been implicated in playing an important role in the
pathogenesis of experimental myopia. We investigated the association of disruptions of COL1A1 gene with high myopia by analyzing the frequency of ten SNPs in a Japanese population of 330 subjects with high myopia of
−9.25 D or less and 330 randomized controls without high myopia. Two SNPs (rs2075555 and rs2269336) were significantly associated
with high myopia (P < 0.05, Pc < 0.1). Two different haplotype blocks in COL1A1 were observed by the pair-wise linkage disequilibrium between the SNPs. The frequency of GGC/GGC diplotype constructed by
the three SNPs (rs2075555, rs2269336, rs1107946) was significantly high (OR = 1.6) and associated with high myopia (P = 0.028, Pc< 0.084). Together our results provide the first evidence for COL1A1 as a gene associated with high myopia. 相似文献