全文获取类型
收费全文 | 1269篇 |
免费 | 79篇 |
出版年
2020年 | 8篇 |
2019年 | 12篇 |
2016年 | 19篇 |
2015年 | 30篇 |
2014年 | 27篇 |
2013年 | 52篇 |
2012年 | 82篇 |
2011年 | 59篇 |
2010年 | 39篇 |
2009年 | 42篇 |
2008年 | 48篇 |
2007年 | 55篇 |
2006年 | 57篇 |
2005年 | 57篇 |
2004年 | 59篇 |
2003年 | 58篇 |
2002年 | 55篇 |
2001年 | 18篇 |
2000年 | 12篇 |
1999年 | 22篇 |
1998年 | 24篇 |
1997年 | 17篇 |
1996年 | 16篇 |
1995年 | 28篇 |
1994年 | 17篇 |
1993年 | 19篇 |
1992年 | 12篇 |
1991年 | 12篇 |
1990年 | 9篇 |
1989年 | 15篇 |
1988年 | 11篇 |
1986年 | 8篇 |
1985年 | 10篇 |
1983年 | 9篇 |
1981年 | 11篇 |
1980年 | 9篇 |
1975年 | 8篇 |
1973年 | 10篇 |
1972年 | 9篇 |
1968年 | 8篇 |
1966年 | 10篇 |
1965年 | 10篇 |
1963年 | 7篇 |
1962年 | 11篇 |
1959年 | 8篇 |
1958年 | 9篇 |
1956年 | 9篇 |
1952年 | 8篇 |
1939年 | 9篇 |
1937年 | 8篇 |
排序方式: 共有1348条查询结果,搜索用时 15 毫秒
961.
962.
Crystallographic investigation of peptide binding sites in the N-domain of the ClpA chaperone 总被引:2,自引:0,他引:2
Escherichia coli ClpA, an Hsp100/Clp chaperone and an integral component of the ATP-dependent ClpAP protease, participates in the dissolution and degradation of regulatory proteins and protein aggregates. ClpA consists of three functional domains: an N-terminal domain and two ATPase domains, D1 and D2. The N-domain is attached to D1 by a mobile linker and is made up of two tightly bound, identically folded alpha-helical bundles related by a pseudo 2-fold symmetry. Between the halves of the pseudo-dimer is a large flexible acidic loop that becomes better ordered upon binding of the small adaptor protein, ClpS. We have identified a number of structural features in the N-domain, including a Zn(++) binding motif, several interfaces for binding to ClpS, and a prominent hydrophobic surface area that binds peptides in different configurations. These structural motifs may contribute to binding of protein or peptide substrates with weak affinity and broad specificity. Kinetic studies comparing wild-type ClpA to a mutant ClpA with its N-domain deleted show that the N-domains contribute to the binding of a non-specific protein substrate but not of a folded substrate with the specific SsrA recognition tag. A functional model is proposed in which the N-domains in ClpA function as tentacles to weakly hold on to proteins thereby enhancing local substrate concentration. 相似文献
963.
Bareiss PM Metzger M Sohn K Rupp S Frick JS Autenrieth IB Lang F Schwarz H Skutella T Just L 《Histochemistry and cell biology》2008,129(6):795-804
Together with animal experiments, organotypical cell cultures are important models for analyzing cellular interactions of the mucosal epithelium and pathogenic mechanisms in the gastrointestinal tract. Here, we introduce a three-dimensional culture model from the adult mouse colon for cell biological investigations in an in vivo-like environment. These explant cultures were cultured for up to 2 weeks and maintained typical characteristics of the intestinal mucosa, including a high-prismatic epithelium with specific epithelial cell-to-cell connections, a basal lamina and various connective tissue cell types, as analyzed with immunohistological and electron microscopic methods. The function of the epithelium was tested by treating the cultures with dexamethasone, which resulted in a strong upregulation of the serum- and glucocorticoid-inducible kinase 1 similar to that found in vivo. The culture system was investigated in infection experiments with the fungal pathogen Candida albicans. Wildtype but not Deltacph1/Deltaefg1-knockout Candida adhered to, penetrated and infiltrated the epithelial barrier. The results demonstrate the potential usefulness of this intestinal in vitro model for studying epithelial cell-cell interactions, cellular signaling and microbiological infections in a three-dimensional cell arrangement. 相似文献
964.
Expression of N-myristoyltransferase in Human Brain Tumors 总被引:1,自引:0,他引:1
Lu Y Selvakumar P Ali K Shrivastav A Bajaj G Resch L Griebel R Fourney D Meguro K Sharma RK 《Neurochemical research》2005,30(1):9-13
N-myristoylation is a process of covalent irreversible protein modification that promotes association of proteins with membranes. Based on our previous findings of elevated N-myristoyltransferase (NMT) activity in colonic epithelial neoplasms that appears at an early stage in colonic carcinogenesis, together with elevated NMT expression in human colorectal and gallbladder carcinomas, we investigated NMT activity and protein expression of NMT1 and NMT2 in human brain tumors and documented elevated NMT activity and higher protein expressions. For the first time, we have demonstrated that NMT has the potential to be used as a marker of human brain tumors. However, further studies with larger number of patients are required to establish its role as a complementary diagnostic tool. This finding has significant implications for further understanding of biological mechanisms involved in tumorigenesis, as well as for diagnosis and therapy of human brain tumors. 相似文献
965.
Clp protease complexes and their diversity in chloroplasts 总被引:5,自引:0,他引:5
Anna Sokolenko Silvia Lerbs-Mache Lothar Altschmied Reinhold G. Herrmann 《Planta》1998,207(2):286-295
The Clp proteases represent a large, ancient ATP-dependent protease family which in higher plants is known to be located
in chloroplasts. The soluble, presumably multisubunit, enzyme of the organelle stroma is of dual genetic origin. It consists
of a nuclear-encoded, regulatory subunit ClpC, which is an ATPase, and a plastid-encoded proteolytic subunit ClpP, which is
a serine protease. An additional, nuclear-encoded proteolytic subunit resembling ClpP has been recently reported from tomato
(Schaller and Ryan, 1995 plant gene Register 95–00). We demonstrate that in both tomato Lycopersicon esculentum Mill. and Arabidopsis thaliana, (L.) Heynh. the nuclear-encoded ClpP (nClpP) is made as a precursor molecule that can be imported into isolated intact chloroplasts
of spinach (Spinacia oleracea L.) and processed in two or three steps, respectively, to the size of the authentic protein. Furthermore, both gel electrophoresis
under non-denaturing conditions and size-exclusion chromatography verified that the three proteins can form distinct heteromeric
supramolecular complexes of approximately 860, 1380 and 1700 kDa (probably also of 600 kDa) molecular mass. The size ranges
of the former two are reminiscent of those of Clp complexes described from Escherichia coli. In addition, various complexes between 160 and 560 kDa are detectable with the individual components. Both the processing
“intermediates” and the mature nClpP are found in assembled form.
Received: 11 March 1998 / Accepted: 8 July 1998 相似文献
966.
967.
A New Shiga Toxin 2 Variant (Stx2f) from Escherichia coli Isolated from Pigeons 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Herbert Schmidt Jürgen Scheef Stefano Morabito Alfredo Caprioli Lothar H. Wieler Helge Karch 《Applied microbiology》2000,66(3):1205-1208
We have isolated Shiga toxin (Stx)-producing Escherichia coli (STEC) strains from the feces of feral pigeons which contained a new Stx2 variant gene designated stx2f. This gene is most similar to sltIIva of patient E. coli O128:B12 isolate H.I.8. Stx2f reacted only weakly with commercial immunoassays. The prevalence of STEC organisms carrying the stx2f gene in pigeon droppings was 12.5%. The occurrence of a new Stx2 variant in STEC from pigeons enlarges the pool of Stx2 variants and raises the question whether horizontal gene transfer to E. coli pathogenic to humans may occur. 相似文献
968.
Rapid Recovery from Eutrophication of a Stratified Lake by Disruption of Internal Nutrient Load 总被引:2,自引:0,他引:2
Thomas Mehner Markus Diekmann Thomas Gonsiorczyk Peter Kasprzak Rainer Koschel Lothar Krienitz Marion Rumpf Michael Schulz Gerlinde Wauer 《Ecosystems》2008,11(7):1142-1156
Restoration of anthropogenically eutrophied lake ecosystems is difficult due to feedback mechanisms that stabilize the trophically
degraded state. Here, we show rapid recovery of a eutrophic stratified lake in response to multiple restoration that targeted
the feedback mechanisms of high external and internal nutrient loads, lack of a trophic cascade, and lack of structured littoral
habitats. Lake Tiefwarensee (Germany) was exposed to aluminium and calcium treatment and fisheries management over 5 years.
Within this period, in-lake phosphorus concentrations declined by more than 80%, and transparency, zooplankton biomass and
fish assemblage structure and biomass responded immediately and almost linearly to the reduction in phosphorus concentrations.
Phytoplankton biomass and chlorophyll a (chl a) concentrations likewise decreased in response to restoration, but the declining
trend was interrupted by one recovery year with unusually high phytoplankton biomasses. The zooplankton:phytoplankton biomass
ratio and the chl a:phosphorus ratio approached values observed in other stratified lakes during natural recovery from eutrophication.
The slow response of Tiefwarensee to the reduction of external load, and the quick response to the chemical treatment suggest
that the disruption of internal P recycling and loading was the decisive restoration measure in Tiefwarensee. The external
load reduction was a necessary but not sufficient measure, at least in the short-term, whereas the low-effort fisheries management
was of minor importance. A comparison with other case studies confirms that measures aiming to inactivate phosphorus are the
most efficient approaches to restore stratified lakes in the short-term, but a shift to a permanent near-pristine state is
possible only by additional P input control.
Author Contributions: T.M. designed the study, analyzed data, and wrote the paper. M.D. analyzed data. T.G. analyzed data.
P.K. designed the study and analyzed data. R.K. conceived of and designed the study. L.K, M.R. and M.S. analyzed data. G.W.
contributed new methods, analyzed data and wrote parts of the paper. All authors contributed to writing the final version. 相似文献
969.
Guo F Esser L Singh SK Maurizi MR Xia D 《The Journal of biological chemistry》2002,277(48):46753-46762
Substrate selectivity and proteolytic activity for the E. coli ATP-dependent protease, ClpAP, is modulated by an adaptor protein, ClpS. ClpS binds to ClpA, the regulatory component of the ClpAP complex. We report the crystal structure of ClpS in complex with the isolated N-terminal domain of ClpA in two different crystal forms at 2.3- and 3.3-A resolution. The ClpS structure forms an alpha/beta-sandwich and is topologically analogous to the C-terminal domain of the ribosomal protein L7/L12. ClpS contacts two surfaces on the N-terminal domain in both crystal forms; the more extensive interface was shown to be favored in solution by protease protection experiments. The N-terminal 20 residues of ClpS are not visible in the crystal structures; the removal of the first 17 residues produces ClpSDeltaN, which binds to the ClpA N-domain but no longer inhibits ClpA activity. A zinc binding site involving two His and one Glu residue was identified crystallographically in the N-terminal domain of ClpA. In a model of ClpS bound to hexameric ClpA, ClpS is oriented with its N terminus directed toward the distal surface of ClpA, suggesting that the N-terminal region of ClpS may affect productive substrate interactions at the apical surface or substrate entry into the ClpA translocation channel. 相似文献
970.