全文获取类型
收费全文 | 1802篇 |
免费 | 117篇 |
专业分类
1919篇 |
出版年
2024年 | 2篇 |
2023年 | 13篇 |
2022年 | 28篇 |
2021年 | 72篇 |
2020年 | 34篇 |
2019年 | 44篇 |
2018年 | 58篇 |
2017年 | 40篇 |
2016年 | 63篇 |
2015年 | 109篇 |
2014年 | 101篇 |
2013年 | 148篇 |
2012年 | 185篇 |
2011年 | 203篇 |
2010年 | 104篇 |
2009年 | 96篇 |
2008年 | 116篇 |
2007年 | 92篇 |
2006年 | 88篇 |
2005年 | 77篇 |
2004年 | 80篇 |
2003年 | 59篇 |
2002年 | 49篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 7篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
排序方式: 共有1919条查询结果,搜索用时 15 毫秒
81.
Christine App Jana Knop Thomas Huff Angela Seebahn Cord-Michael Becker Federica Iavarone Massimo Castagnola Ewald Hannappel 《Analytical biochemistry》2014
A new photoactivatable trifunctional cross-linker, cBED (cadaverine-2-[6-(biotinamido)-2-(p-azidobenzamido) hexanoamido]ethyl-1,3′-dithiopropionate), was synthesized by chemical conversion of sulfo-SBED (sulfosuccinimidyl-2-[6-(biotinamido)-2-(p-azidobenzamido) hexanoamido]ethyl-1,3′-dithiopropionate) with cadaverine. This cross-linker was purified by reversed-phase high-performance liquid chromatography (RP–HPLC) and characterized using matrix-assisted laser desorption/ionization time-of-flight (MALDI–TOF) analysis. cBED is based on sulfo-SBED that has a photoactivatable azido group, a cleavable disulfide bond for label transfer methods, and a biotin moiety for highly sensitive biotin/avidin detection. By ultraviolet (UV) light, the azido group is converted to a reactive nitrene, transforming transient bindings of interacting structures to covalent bonds. In contrast to the sulfo-N-hydroxysuccinimide (sulfo-NHS) moiety of sulfo-SBED, which attaches quite unspecifically to amino groups, cBED includes a cadaverine moiety that can be attached by transglutaminase more specifically to certain glutamine residues. For instance, thymosin β4 can be labeled with cBED using tissue transglutaminase. By high-resolution HPLC/ESI–MS (electrospray ionization–mass spectrometry) and tandem MS (MS/MS) of the trypsin digest, it was established that glutamine residues at positions 23 and 36 were labeled, whereas Q39 showed no reactivity. The covalent binding of cBED to thymosin β4 did not influence its G-actin sequestering activity, and the complex could be used to identify new interaction partners. Therefore, cBED can be used to better understand the multifunctional role of thymosin β4 as well as of other proteins and peptides. 相似文献
82.
Carbapenem-resistant gram-negative pathogens represent an emerging threat to the management of hospital-acquired infections. Although the isolation of carbapenem-resistant enterobacteriaceae remains unusual, the frequency of carbapenemases producing Klebsiella pneumoniae is increasing in different geographic regions: the majority of isolates has been collected in the USA, but recently KPC-producing K. pneumoniae were reported from China, Israel, Greece, France, Norway and Sweden. We report a KPC 1-producing K. pneumoniae isolate from Italy. This datum enlarges the geographical area where the KPC-producing K. pneumoniae strains are diffuse. 相似文献
83.
Federica Sinibaldi Barry D. Howes Maria Cristina Piro Fabio Polticelli Cecilia Bombelli Tommaso Ferri Massimo Coletta Giulietta Smulevich Roberto Santucci 《Journal of biological inorganic chemistry》2010,15(5):689-700
Two models have been proposed to explain the interaction of cytochrome c with cardiolipin (CL) vesicles. In one case, an acyl chain of the phospholipid accommodates into a hydrophobic channel of
the protein located close the Asn52 residue, whereas the alternative model considers the insertion of the acyl chain in the
region of the Met80-containing loop. In an attempt to clarify which proposal offers a more appropriate explanation of cytochrome
c–CL binding, we have undertaken a spectroscopic and kinetic study of the wild type and the Asn52Ile mutant of iso-1-cytochrome
c from yeast to investigate the interaction of cytochrome c with CL vesicles, considered here a model for the CL-containing mitochondrial membrane. Replacement of Asn52, an invariant
residue located in a small helix segment of the protein, may provide data useful to gain novel information on which region
of cytochrome c is involved in the binding reaction with CL vesicles. In agreement with our recent results revealing that two distinct transitions
take place in the cytochrome c–CL binding reaction, data obtained here support a model in which two (instead of one, as considered so far) adjacent acyl
chains of the liposome are inserted, one at each of the hydrophobic sites, into the same cytochrome c molecule to form the cytochrome c–CL complex. 相似文献
84.
Francisca Reyes Gabriel León Maribel Donoso Federica Brandizzí Andreas P.M. Weber Ariel Orellana 《The Plant journal : for cell and molecular biology》2010,61(3):423-435
Uridine 5′‐diphosphate (UDP)‐glucose is transported into the lumen of the endoplasmic reticulum (ER), and the Arabidopsis nucleotide sugar transporter AtUTr1 has been proposed to play a role in this process; however, different lines of evidence suggest that another transporter(s) may also be involved. Here we show that AtUTr3 is involved in the transport of UDP‐glucose and is located at the ER but also at the Golgi. Insertional mutants in AtUTr3 showed no obvious phenotype. Biochemical analysis in both AtUTr1 and AtUTr3 mutants indicates that uptake of UDP‐glucose into the ER is mostly driven by these two transporters. Interestingly, the expression of AtUTr3 is induced by stimuli that trigger the unfolded protein response (UPR), a phenomenon also observed for AtUTr1, suggesting that both AtUTr1 and AtUTr3 are involved in supplying UDP‐glucose into the ER lumen when misfolded proteins are accumulated. Disruption of both AtUTr1 and AtUTr3 causes lethality. Genetic analysis showed that the atutr1 atutr3 combination was not transmitted by pollen and was poorly transmitted by the ovules. Cell biology analysis indicates that knocking out both genes leads to abnormalities in both male and female germ line development. These results show that the nucleotide sugar transporters AtUTr1 and AtUTr3 are required for the incorporation of UDP‐glucose into the ER, are essential for pollen development and are needed for embryo sac progress in Arabidopsis thaliana. 相似文献
85.
Lucia Marti Giovanni Stefano Kentaro Tamura Chris Hawes Luciana Renna Michael A. Held Federica Brandizzi 《The Plant journal : for cell and molecular biology》2010,63(6):901-913
A central question in cell biology is how the identity of organelles is established and maintained. Here, we report on GOLD36, an EMS mutant identified through a screen for partial displacement of the Golgi marker, ST‐GFP, to other organelles. GOLD36 showed partial distribution of ST‐GFP into a modified endoplasmic reticulum (ER) network, which formed bulges and large skein‐like structures entangling Golgi stacks. GOLD36 showed defects in ER protein export as evidenced by our observations that, besides the partial retention of Golgi markers in the ER, the trafficking of a soluble bulk‐flow marker to the cell surface was also compromised. Using a combination of classical mapping and next‐generation DNA sequencing approaches, we linked the mutant phenotype to a missense mutation of a proline residue in position 80 to a leucine residue in a small endomembrane protein encoded by the gold36 locus ( At1g54030 ). Subcellular localization analyses indicated that GOLD36 is a vacuolar protein and that its mutated form is retained in the ER. Interestingly also, a gold36 knock‐out mutant mirrored the GOLD36 subcellular phenotype. These data indicate that GOLD36 is a protein destined to post‐ER compartments and suggest that its export from the ER is a requirement to ensure steady‐state maintenance of the organelle’s organization and functional activity in relation to other secretory compartments. We speculate that GOLD36 may be a factor that is necessary for ER integrity because of its ability to limit deleterious effects of other secretory proteins on the ER. 相似文献
86.
The identification of a series of novel, soluble non-peptidic neuropeptide Y Y2 receptor antagonists
Lunniss GE Barnes AA Barton N Biagetti M Bianchi F Blowers SM Caberlotto LL Emmons A Holmes IP Montanari D Norris R Puckey GV Walters DJ Watson SP Willis J 《Bioorganic & medicinal chemistry letters》2010,20(24):7341-7344
The identification and subsequent optimisation of a selective non-peptidic NPY Y2 antagonist series is described. This led to the development of amine 2, a selective, soluble NPY Y2 receptor antagonist with enhanced CNS exposure. 相似文献
87.
Cossu F Malvezzi F Canevari G Mastrangelo E Lecis D Delia D Seneci P Scolastico C Bolognesi M Milani M 《Protein science : a publication of the Protein Society》2010,19(12):2418-2429
Inhibitor of apoptosis proteins (IAPs) are negative regulators of apoptosis. As IAPs are overexpressed in many tumors, where they confer chemoresistance, small molecules inactivating IAPs have been proposed as anticancer agents. Accordingly, a number of IAP-binding pro-apoptotic compounds that mimic the sequence corresponding to the N-terminal tetrapeptide of Smac/DIABLO, the natural endogenous IAPs inhibitor, have been developed. Here, we report the crystal structures of the BIR3 domain of cIAP1 in complex with Smac037, a Smac-mimetic known to bind potently to the XIAP-BIR3 domain and to induce degradation of cIAP1, and in complex with the novel Smac-mimetic compound Smac066. Thermal stability and fluorescence polarization assays show the stabilizing effect and the high affinity of both Smac037 and Smac066 for cIAP1- and cIAP2-BIR3 domains. 相似文献
88.
Federica Della Rovere Chiara A Airoldi Giuseppina Falasca Alessandra Ghiani Laura Fattorini Sandra Citterio Martin Kater Maria Maddalena Altamura 《Plant signaling & behavior》2010,5(6):677-680
Proteins containing bromodomains are capable of binding to acetylated histone tails and have a role in recognizing and deciphering acetylated chromatin. Plant BET proteins contain one bromodomain. Twelve BET-encoding genes have been identified in the Arabidopsis genome. Two of these genes have been functionally characterized, one shows a role in seed germination, the other is involved in the establishment of leaf shape. Recently, we characterized a third AtBET gene, named GTE4. We demonstrated that GTE4 is involved in the activation and maintenance of cell division in the meristems and by this controls cell numbers in differentiated organs. Moreover, the quiescent center (QC) identity is partially lost in the apex of the primary root of gte4 mutant, and there is a premature switch from mitosis to endocycling. Genes involved in the retinoblastoma (RB)-E2F pathway, which is important for coupling cell division and cell differentiation in plants and animals, were either up or downregulated in the gte4 mutant. In this report we also show that the defect in germination observed in gte4 mutant seeds is not rescued by the action of GA3. Further the root pole of the mutant embryo shows irregular cytokinesis in the procambial stem cells, and the QC of the lateral root shows a partial, but not transient, loss of QC identity. These additional results reinforce the importance of GTE4 in the control of cell proliferation.Key words: arabidopsis, BET bromodomain, cell cycle, E2F, germination 相似文献
89.
Federica Susta Davide Chiasserini Katia Fettucciari Pier Luigi Orvietani Flavia Quotadamo Rosina Noce Andrea Bartoli Pierfrancesco Marconi Lanfranco Corazzi Luciano Binaglia 《Proteomics》2010,10(11):2099-2112
Protein expression changes induced in thioglycolate‐elicited peritoneal murine macrophages (MΦ) by infection with type III Group B Streptococcus (GBS) are described. Proteins from control MΦ and MΦ incubated 2 h with live or heat‐inactivated GBS were separated by 2‐DE. Proteins whose expression was significantly different in infected MΦ, as compared with control cells, were identified by MS/MS analysis. Changes in the expression level of proteins involved in both positive and negative modulation of phagocytic functions, stress response and cell death were induced in MΦ by GBS infection. In particular, expression of enzymes playing a key role in production of reactive oxygen species was lowered in GBS‐infected MΦ. Significant alterations in the expression of some metabolic enzymes were also observed, most of the glycolytic and of the pentose‐cycle enzymes being down‐regulated in MΦ infected with live GBS. Finally, evidence was obtained that GBS infection affects the expression of enzymes or enzyme subunits involved in ATP synthesis and in adenine nucleotides interconversion processes. 相似文献
90.
The spring–summer photosynthetic behaviour of Pistacia lentiscus, a spontaneous evergreen bush of the Mediterranean macchia, was followed during two consecutive years. Outdoor measurements
were carried out monthly in the period from May to September in the years 2004 and 2005. Mean values of net photosynthesis
(P
N) of external tests show a typical daily trend: a rise until the maximum followed by a decline of assimilation with lower
values maintained until the end of day. External data were validated by light-response curves, obtained under different thermal
regimes in controlled conditions. External trials and measures in controlled conditions confirm an elevated photosynthetic
activity below 30°C and a decrease over that limit. The results obtained evidence that the CO2 assimilation of the P. lentiscus is influenced by stressful temperatures. The ecophysiological response to this limiting factor is an adaptation that concentrates
on the photosynthetic activity in the hours of the day and in the periods of the year in which temperatures are more favourable. 相似文献