全文获取类型
收费全文 | 302篇 |
免费 | 43篇 |
出版年
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2015年 | 4篇 |
2014年 | 10篇 |
2013年 | 12篇 |
2012年 | 3篇 |
2011年 | 13篇 |
2010年 | 9篇 |
2009年 | 6篇 |
2008年 | 13篇 |
2007年 | 21篇 |
2006年 | 31篇 |
2005年 | 13篇 |
2004年 | 16篇 |
2003年 | 21篇 |
2002年 | 14篇 |
2001年 | 15篇 |
2000年 | 13篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 7篇 |
1995年 | 4篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 11篇 |
1989年 | 9篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 7篇 |
1985年 | 1篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1970年 | 3篇 |
1968年 | 1篇 |
1958年 | 1篇 |
1905年 | 1篇 |
排序方式: 共有345条查询结果,搜索用时 625 毫秒
31.
The movements of the basis of maxilla 2 in Palaemon adspersus were examined using macro-video recordings, and the morphology of its setae was examined using both scanning and transmission electron microscopy. The basis of maxilla 2 performs stereotypical movements in the latero-medial plane and gently touches the food with a frequency of 3-5 Hz. The medial rim of the basis of maxilla 2 carries three types of seta. Type 1 is serrate, type 2 and 3 are serrulate, and type 2 has a prominent terminal pore. Type 2 is innervated by 18-25 sensory cells whose cilia protrude through the terminal pore and are in direct contact with the external environment. The structure of type 2 setae indicates that they are mainly gustatory, although still bimodal due to their innervation by presumed chemosensory and mechanosensory neurons. Distally, the three types of setae have a complex arrangement of the cuticle involving water-filled canals, which may serve to improve flexibility. Type 1 and 3 setae have fewer sensory cells (4-9) but probably also have a bimodal sensory function. The function of type 1 setae is probably to protect type 2 setae, while type 3 setae might serve to groom the ventral side of the basis of maxilla 1. 相似文献
32.
Exoenzyme T of Pseudomonas aeruginosa elicits cytotoxicity without interfering with Ras signal transduction 总被引:3,自引:1,他引:2
Sundin C Henriksson ML Hallberg B Forsberg A Frithz-Lindsten E 《Cellular microbiology》2001,3(4):237-246
One virulence strategy used by the opportunistic pathogen Pseudomonas aeruginosa is to target toxic proteins into eukaryotic cells by a type III secretion mechanism. Two of these proteins, ExoS and ExoT, show 75% homology on amino acid level. However, compared with ExoS, ExoT exhibits highly reduced ADP-ribosylating activity and the role of ExoT in pathogenesis is poorly understood. To study the biological effect of ExoT, we used a strategy by which ExoT was delivered into host cells by the heterologous type III secretion system of Yersinia pseudotuberculosis . ExoT was found to induce a rounded cell morphology and to mediate disruption of actin microfilaments, similar to that induced by an ADP-ribosylation defective ExoS (E381A) and the related cytotoxin YopE of Y. pseudotuberculosis . In contrast to ExoS, ExoT had no major effect on cell viability and did not modify or inactivate Ras by ADP-ribosylation in vivo . However, similar to ExoS and YopE, ExoT exhibited GAP (GTPase activating protein) activity on RhoA GTPase in vitro . Interestingly, ExoT(R149K), deficient for GAP activity, still caused a morphological change of HeLa cells. Based on our findings, we suggest that the ADP-ribosylating activity of ExoT target another, as yet unidentified, host protein that is distinct from Ras. 相似文献
33.
Dukuzumuremyi JM Rosqvist R Hallberg B Akerström B Wolf-Watz H Schesser K 《The Journal of biological chemistry》2000,275(45):35281-35290
The pathogenic yersiniae inject proteins directly into eukaryotic cells that interfere with a number of cellular processes including phagocytosis and inflammatory-associated host responses. One of these injected proteins, the Yersinia protein kinase A (YpkA), has previously been shown to affect the morphology of cultured eukaryotic cells as well as to localize to the plasma membrane following its injection into HeLa cells. Here it is shown that these activities are mediated by separable domains of YpkA. The amino terminus, which contains the kinase domain, is sufficient to localize YpkA to the plasma membrane while the carboxyl terminus of YpkA is required for YpkAs morphological effects. YpkAs carboxyl-terminal region was found to affect the levels of actin-containing stress fibers as well as block the activation of the GTPase RhoA in Yersinia-infected cells. We show that the carboxyl-terminal region of YpkA, which contains sequences that bear similarity to the RhoA-binding domains of several eukaryotic RhoA-binding kinases, directly interacts with RhoA as well as Rac (but not Cdc42) and displays a slight but measurable binding preference for the GDP-bound form of RhoA. Surprisingly, YpkA binding to RhoA(GDP) affected neither the intrinsic nor guanine nucleotide exchange factor-mediated GDP/GTP exchange reaction suggesting that YpkA controls activated RhoA levels by a mechanism other than by simply blocking guanine nucleotide exchange factor activity. We go on to show that YpkAs kinase activity is neither dependent on nor promoted by its interaction with RhoA and Rac but is, however, entirely dependent on heat-sensitive eukaryotic factors present in HeLa cell extracts and fetal calf serum. Collectively, our data show that YpkA possesses both similarities and differences with the eukaryotic RhoA/Rac-binding kinases and suggest that the yersiniae utilize the Rho GTPases for unique activities during their interaction with eukaryotic cells. 相似文献
34.
Effects of aging and caloric restriction on IGF-I, IGF-I receptor, IGFBP-3 and IGFBP-4 gene expression in the rat stomach and colon 总被引:2,自引:0,他引:2
The purpose of this study was to determine the effects of aging and caloric restriction (CR) on insulin-like growth factor-I (IGF-I), IGF-I receptor (IGF-IR), IGF-binding protein-3 (IGFBP-3) and IGFBP-4 expression in the stomach and colon of male Fischer 344 rats. Stomach and colonic RNA were prepared from ad libitum (AL) fed or long-term CR rats. Stomach IGF-I, IGFBP-3 and IGFBP-4 mRNA levels increased significantly (P=0.05), while colonic IGF-I mRNA levels were unchanged in aged AL rats. In aged CR rats, stomach IGFBP-3 mRNA levels decreased. Stomach and colonic IGF-IR mRNA levels declined with aging in AL and CR rats (P=0.05). Colonic IGFBP-3 mRNA levels decreased significantly with aging in AL rats. There were no changes in colonic IGFBP-4 mRNA levels in aged AL or CR rats. Increased expression of stomach IGF-I, IGFBP-3 and IGFBP-4 in aged AL rats suggests that the stomach attempts to preserve IGF activity by increasing local expression of IGF-I and IGFBPs. Because the aging colon has a propensity to develop cancer, it may adapt to increased colonic IGF-I expression by reducing IGF-IR and IGFBP-3 expression. Additionally, CR lowers colonic IGF-I expression in aged rats (24 months) which may also be a protective adaptive mechanism. 相似文献
35.
Ecophysiology of Fe-cycling bacteria in acidic sediments 总被引:2,自引:0,他引:2
Lu S Gischkat S Reiche M Akob DM Hallberg KB Küsel K 《Applied and environmental microbiology》2010,76(24):8174-8183
Using a combination of cultivation-dependent and -independent methods, this study aimed to elucidate the diversity of microorganisms involved in iron cycling and to resolve their in situ functional links in sediments of an acidic lignite mine lake. Using six different media with pH values ranging from 2.5 to 4.3, 117 isolates were obtained that grouped into 38 different strains, including 27 putative new species with respect to the closest characterized strains. Among the isolated strains, 22 strains were able to oxidize Fe(II), 34 were able to reduce Fe(III) in schwertmannite, the dominant iron oxide in this lake, and 21 could do both. All isolates falling into the Gammaproteobacteria (an unknown Dyella-like genus and Acidithiobacillus-related strains) were obtained from the top acidic sediment zones (pH 2.8). Firmicutes strains (related to Bacillus and Alicyclobacillus) were only isolated from deep, moderately acidic sediment zones (pH 4 to 5). Of the Alphaproteobacteria, Acidocella-related strains were only isolated from acidic zones, whereas Acidiphilium-related strains were isolated from all sediment depths. Bacterial clone libraries generally supported and complemented these patterns. Geobacter-related clone sequences were only obtained from deep sediment zones, and Geobacter-specific quantitative PCR yielded 8 × 10(5) gene copy numbers. Isolates related to the Acidobacterium, Acidocella, and Alicyclobacillus genera and to the unknown Dyella-like genus showed a broad pH tolerance, ranging from 2.5 to 5.0, and preferred schwertmannite to goethite for Fe(III) reduction. This study highlighted the variety of acidophilic microorganisms that are responsible for iron cycling in acidic environments, extending the results of recent laboratory-based studies that showed this trait to be widespread among acidophiles. 相似文献
36.
van Beers JJ Raijmakers R Alexander LE Stammen-Vogelzangs J Lokate AM Heck AJ Schasfoort RB Pruijn GJ 《Arthritis research & therapy》2010,12(6):R219
Introduction
Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using a new methodology. 相似文献37.
Cultivation-based and molecular approaches were used to characterize the phylogenetic composition and structure of the microbial community in an extremely acidic (pH 2.0) acid mine drainage (AMD) associated with Pb/Zn mine tailings that were undergoing vigorous acid generation. Acidophilic bacteria were isolated and enumerated on solid media, and were found to be restricted to isolates related to Acidithiobacillus ferrooxidans and Acidiphilium cryptum. By contrast, cloning and phylogenetic analysis of 16S rRNA genes revealed that, although low in total taxonomically distinct groups, the tailings AMD ecosystem harbored a wide range of phylogenetically diverse microbes. Of the 141 clones examined, 104 were phylogenetically affiliated with the recently discovered, iron-oxidizing Leptospirillum group III within the Nitrospira. It thus appears that iron serves as the major electron donor in this habitat. Thirty clones were affiliated with the Proteobacteria, half of which belonged to organisms related to Alphaproteobacteria species capable of ferric iron reduction. Other clones were grouped with Betaproteobacteria and Gammaproteobacteria (six clones each), and even with Deltaproteobacteria (three clones), a subdivision with anaerobic sulfate or metal (iron) reduction as the predominant physiological trait of its members. Finally, four clones were clustered within the Firmicutes and the Acidobacteria. Approximately half of the sequence types representing the majority of the total clones fell into lineages that are poorly represented by cultured organisms or have thus far been represented by only a few environmental sequences. Thus, the present study extends our knowledge of the biodiversity of microorganisms populating highly acidic AMD environments. 相似文献
38.
The misuse of anabolic androgenic steroids (AAS) seems to produce profound effects on the central nervous system, leading to aggressive behavior and increased sensitivity to other drugs of abuse. The present study addresses the effect on the enzymatic transformation, here called dynorphin converting enzyme-like activity. The formation of the mu/delta opioid peptide receptor-preferring Leu-enkephalin-Arg(6) from the kappa opioid peptide receptor-preferring dynorphin A was measured in rats treated with nandrolone decanoate. Significant variations in enzymatic transformation were observed in several brain regions. An altered receptor activation profile in these regions may be one contributory factor behind AAS-induced personality changes. 相似文献
39.
Thorstensson F Wångsell F Kvarnström I Vrang L Hamelink E Jansson K Hallberg A Rosenquist S Samuelsson B 《Bioorganic & medicinal chemistry》2007,15(2):827-838
Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-l-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored in the P1-position and in the P2-position the hydroxyl group of the cyclopentene template was substituted with 7-methoxy-2-phenyl-quinolin-4-ol. The P3/P4-positions were then optimized from a set of six amino acid derivatives. All inhibitors were evaluated in an in vitro assay using the full-length NS3 protease. Several potent inhibitors were identified, the most promising exhibiting a K(i) value of 1.1nM. 相似文献
40.
Edling CE Hallberg B 《The international journal of biochemistry & cell biology》2007,39(11):1995-1998
The receptor tyrosine kinase c-Kit is expressed in hematopoietic stem and progenitor cells and in several non-hematopoietic tissues. In the hematopoietic system, c-Kit is critical for proliferation, survival and differentiation. During recent years exploration of the signalling pathways downstream of this receptor has yielded significant new insights in the field. In this review, we will summarise the c-Kit background, structure, downstream signalling and medical significance with particular focus on its role in hematopoietic progenitor cells and mast cells. 相似文献