全文获取类型
收费全文 | 1063篇 |
免费 | 50篇 |
出版年
2022年 | 5篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 14篇 |
2016年 | 14篇 |
2015年 | 28篇 |
2014年 | 23篇 |
2013年 | 38篇 |
2012年 | 53篇 |
2011年 | 53篇 |
2010年 | 32篇 |
2009年 | 25篇 |
2008年 | 53篇 |
2007年 | 45篇 |
2006年 | 56篇 |
2005年 | 54篇 |
2004年 | 52篇 |
2003年 | 62篇 |
2002年 | 72篇 |
2001年 | 51篇 |
2000年 | 46篇 |
1999年 | 53篇 |
1998年 | 16篇 |
1997年 | 11篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 9篇 |
1993年 | 10篇 |
1992年 | 19篇 |
1991年 | 22篇 |
1990年 | 14篇 |
1989年 | 12篇 |
1988年 | 16篇 |
1987年 | 13篇 |
1986年 | 16篇 |
1985年 | 13篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1973年 | 4篇 |
1970年 | 3篇 |
排序方式: 共有1113条查询结果,搜索用时 93 毫秒
101.
Masakatsu Kamiya Keisuke Oyauchi Yoshinori Sato Takuya Yokoyama Mofei Wang Tomoyasu Aizawa Yasuhiro Kumaki Mineyuki Mizuguchi Kunio Imai Makoto Demura Koichi Suzuki Keiichi Kawano 《Journal of peptide science》2010,16(5):242-248
We previously reported that yamamarin, a pentapeptide with an amidated C‐terminus (DILRG‐NH2) isolated from larvae of the silkmoth, and its palmitoylated analog (C16‐DILRG‐NH2) suppressed proliferation of rat hepatoma (liver cancer) cells. In this study, we investigated the structure–activity relationship of yamamarin by in vitro assay and spectroscopic methods (CD and NMR) for various analogs. The in vitro assay results demonstrated that the chemical structure of the C‐terminal part (‐RG‐NH2) of yamamarin is essential for its activity. The CD and NMR results indicated that yamamarin and its analog adopt predominantly a random coil conformation. Moreover, a comparison of NMR spectra of DILRG‐NH2 and C16‐DILRG‐NH2 revealed that the N‐terminal palmitoyl group of C16‐DILRG‐NH2 did not affect the conformation of the C‐terminal part, which is essential for activity. Together, these results should assist in the design of more sophisticated anticancer drugs. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
102.
Although maternal or uniparental inheritance of mitochondrial genomes is a general rule, biparental inheritance is sometimes
observed in protists and fungi, including yeasts. In yeast, recombination occurs between the mitochondrial genomes inherited
from both parents. Mitochondrial fusion observed in yeast zygotes is thought to set up a space for DNA recombination. In the
last decade, a universal mitochondrial fusion mechanism has been uncovered, using yeast as a model. On the other hand, an
alternative mitochondrial fusion mechanism has been identified in the true slime mold Physarum polycephalum. A specific mitochondrial plasmid, mF, has been detected as the genetic material that causes mitochondrial fusion in P. polycephalum. Without mF, fusion of the mitochondria is not observed throughout the life cycle, suggesting that Physarum has no constitutive mitochondrial fusion mechanism. Conversely, mitochondria fuse in zygotes and during sporulation with
mF. The complete mF sequence suggests that one gene, ORF640, encodes a fusogen for Physarum mitochondria. Although in general, mitochondria are inherited uniparentally, biparental inheritance occurs with specific
sexual crossing in P. polycephalum. An analysis of the transmission of mitochondrial genomes has shown that recombinations between two parental mitochondrial
genomes require mitochondrial fusion, mediated by mF. Physarum is a unique organism for studying mitochondrial fusion. 相似文献
103.
Irie K Furukawa S Kadono T Kawano T 《Zeitschrift für Naturforschung. C, Journal of biosciences》2010,65(11-12):681-687
Some hundred cells of Chlorella-like green algae are naturally enclosed within the cytoplasm of a single cell of green paramecia (Paramecium bursaria). Therefore, P. bursaria serves as an experimental model for studying the nature of endo-symbiosis made up through chemical communication between the symbiotic partners. For studying the mechanism of symbiotic regulations, the materials showing successful symbiosis are widely used. Apart from such successful model materials, some models for symbiotic distortion would be of great interest in order to understand the nature of successful symbiosis. Here, we describe a case of unsuccessful symbiosis causing unregulated growth of algae inside the hosting ciliates. Recently, we have screened some cell lines, from the mass of P. bursaria cells survived after paraquat treatment. The resultant cell lines (designated as KMZ series) show novel and unusual morphological features with heavily darker green colour distinguishable from the original pale green-coloured paramecia. In this type of isolates, endo-symbiotic algae are restricted within one or two dense spherical structures located at the center of the host cells' cytoplasm. Interestingly, this isolate maintains the host cells' circadian mating response which is known as an alga-dependent behaviour in the host cells. In contrast, we discuss that KMZ lacks the host-dependent regulation of algal growth, thus the algal complex often over-grows obviously exceeding the original size of the normal hosting ciliates. Additionally, possible use of this isolate as a novel model for symbiotic cell-to-cell communication is discussed. 相似文献
104.
105.
It is well known that soleus muscle of rat atrophies following spaceflight or hindlimb suspension (Ohira et al., 1992). It is, further, reported that the electromyogram (EMG) of soleus muscle disappears immediately in response to unloading by exposure to actual micro-g environment (Kawano et al., 2002; Leterme and Falempin, 1998) and by hindlimb suspension of rats (Alford et al., 1987; Ohira et al., 2000). However, the EMG level is increased gradually to the control level following 7-10 days of continuous hindlimb suspension (Alford et al., 1987; Ohira, 2000), while muscle atrophy is progressing (Winiarski et al., 1987). We previously reported that reduction of the EMG level of rat soleus in response to actual micro-g environment, created by a parabolic flight of a jet airplane, was closely associated with a decrease of the afferent input recorded at the L5 segmental level of spinal cord (Kawano et al., 2002). However, it is still unclear how the EMG level of soleus muscle adapts to unloading condition. The current study was performed to investigate the responses of soleus EMG and both afferent and efferent neurogram at the L5 segmental level of spinal cord to acute (20 seconds) and chronic (14 days) unloading. 相似文献
106.
Peripheral tolerance and the qualitative characteristics of autoreactive T cell clones in primary biliary cirrhosis 总被引:1,自引:0,他引:1
Kawano A Shimoda S Kamihira T Ishikawa F Niiro H Soejima Y Taketomi A Maehara Y Nakamura M Komori A Migita K Ishibashi H Azuma M Gershwin ME Harada M 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(5):3315-3324
Primary biliary cirrhosis is characterized by autoreactive T cells specific for the mitochondrial Ag PDC-E2(163-176). We studied the ability of eight T cell clones (TCC) specific for PDC-E2(163-176) to proliferate or become anergic in the presence of costimulation signals. TCC were stimulated with either human PDC-E2(163-176), an Escherichia coli 2-oxoglutarate dehydrogenase mimic (OGDC-E2(34-47)), or analogs with amino acid substitutions using HLA-matched allogeneic PBMC or mouse L-DR53 fibroblasts as APC. Based on their differential responses to these peptides (human PDC-E2(163-176), E. coli OGDC-E2(34-47)) in the different APC systems, TCC were classified as costimulation dependent or independent. Only costimulation-dependent TCC could become anergic. TCC with costimulation-dependent responses to OGDC-E2 become anergic to PDC-E2 when preincubated with mimic, even if costimulation is independent for PDC-E2(163-176). Anergic TCC produced IL-10. One selected TCC could not become anergic after preincubation with PDC-E2(163-176)-pulsed L-DR53 but became anergic using L-DR53 pulsed with PDC-E2 peptide analogs with a substitution at a critical TCR binding site. TCC that only respond to peptide-pulsed PBMC, but not L-DR53, proliferate with peptide-pulsed CD80/CD86-transfected L-DR53; however, anergy was not induced with peptide-pulsed L-DR53 transfected with only CD80 or CD86. These data highlight that costimulation plays a dominant role in maintaining peripheral tolerance to PBC-specific Ags. They further suggest that, under specific circumstances, molecular mimicry of an autoantigen may restore rather than break peripheral tolerance. 相似文献
107.
Nakano M Takahashi A Sakai Y Kawano M Harada N Mawatari K Nakaya Y 《Letters in applied microbiology》2007,44(6):649-653
AIMS: To evaluate the effect of norepinephrine (NE) and related compounds on the growth of bacteria, we have examined the effect of the neuroendocrine hormone NE and related compounds on the growth of Vibrio parahaemolyticus and other human-pathogenic Vibrio species (Vibrio cholerae, Vibrio vulnificus, and Vibrio mimicus). METHODS AND RESULTS: The effects on bacterial growth were examined using the serum-based medium and viable cells were counted using agar plates. We have shown that NE and its related compounds stimulate growth of V. parahaemolyticus in serum-based medium. This NE-induced growth stimulation was dependent upon the presence of transferrin. NE also stimulated growth of V. mimicus, but not V. cholerae and V. vulnificus. CONCLUSIONS: These results suggest that the Vibrio species differ in their ability to respond to NE. SIGNIFICANCE AND IMPACT OF THE STUDY: It is possible that NE and related compounds modulate the pathogenicity of V. parahaemolyticus and V. mimicus. 相似文献
108.
109.
Honda T Shirasu N Isozaki K Kawano M Shigehiro D Chuman Y Fujita T Nose T Shimohigashi Y 《Bioorganic & medicinal chemistry》2007,15(11):3883-3888
Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 and 4. In order to clarify the role of Phe(3) and Phe(4) in binding to the mu receptor, we synthesized a series of analogs in which Phe(3) and Phe(4) were replaced by various amino acids. It was found that the aromaticity of the Phe-beta-phenyl groups of Phe(3) and Phe(4) is a principal determinant of how strongly it binds to the receptor, although better molecular hydrophobicity reinforces the activity. The receptor binding subsites of Phe(3) and Phe(4) of endomorphin-2 were found to exhibit different structural requirements. The results suggest that [Trp(3)]endomorphin-2 (native endomorphin-1) and endomorphin-2 bind to different receptor subclasses. 相似文献
110.
The solution structure of horseshoe crab antimicrobial peptide tachystatin B with an inhibitory cystine-knot motif. 总被引:1,自引:0,他引:1
Naoki Fujitani Takahide Kouno Taku Nakahara Kenji Takaya Tsukasa Osaki Shun-Ichiro Kawabata Mineyuki Mizuguchi Tomoyasu Aizawa Makoto Demura Shin-Ichiro Nishimura Keiichi Kawano 《Journal of peptide science》2007,13(4):269-279
Tachystatin B is an antimicrobial and a chitin-binding peptide isolated from the Japanese horseshoe crab (Tachypleus tridentatus) consisting of two isopeptides called tachystatin B1 and B2. We have determined their solution structures using NMR experiments and distance geometry calculations. The 20 best converged structures of tachystatin B1 and B2 exhibited root mean square deviations of 0.46 and 0.49 A, respectively, for the backbone atoms in Cys(4)-Arg(40). Both structures have identical conformations, and they contain a short antiparallel beta-sheet with an inhibitory cystine-knot (ICK) motif that is distributed widely in the antagonists for voltage-gated ion channels, although tachystatin B does not have neurotoxic activity. The structural homology search provided several peptides with structures similar to that of tachystatin B. However, most of them have the advanced functions such as insecticidal activity, suggesting that tachystatin B may be a kind of ancestor of antimicrobial peptide in the molecular evolutionary history. Tachystatin B also displays a significant structural similarity to tachystatin A, which is member of the tachystatin family. The structural comparison of both tachystatins indicated that Tyr(14) and Arg(17) in the long loop between the first and second strands might be the essential residues for binding to chitin. 相似文献