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51.
Renato M Salgado Luciane P Capelo Rodolfo R Favaro Jocelyn D Glazier John D Aplin Telma MT Zorn 《Reproductive biology and endocrinology : RB&E》2009,7(1):60
Background
Remodeling of the extracellular matrix is one of the most striking features observed in the uterus during the estrous cycle and after hormone replacement. Versican (VER) is a hyaluronan-binding proteoglycan that undergoes RNA alternative splicing, generating four distinct isoforms. This study analyzed the synthesis and distribution of VER in mouse uterine tissues during the estrous cycle, in ovariectomized (OVX) animals and after 17beta-estradiol (E2) and medroxyprogesterone (MPA) treatments, either alone or in combination. 相似文献52.
53.
Colombo M Ricagno S Barbiroli A Santambrogio C Giorgetti S Raimondi S Bonomi F Grandori R Bellotti V Bolognesi M 《Journal of biochemistry》2011,150(1):39-47
Beta-2 microglobulin (β2m) is the light chain of Class I major histocompatibility complex (MHC-I) complex. β2m is an intrinsically amyloidogenic protein capable of forming amyloid fibrils in vitro and in vivo. β2m displays the typical immunoglobulin-like fold with a disulphide bridge (Cys25-Cys80) cross-linking the two β-sheets. Engineering of the loop comprised between β-strands D and E has shown that mutations in this region affect protein structure, fold stability, folding kinetics and amyloid aggregation properties. Such overall effects have been related to the DE loop backbone structure, which presents a strained conformation in the wild-type (wt) protein, and a type I β-turn in the W60G mutant. Here, we report a biophysical and structural characterization of the K58P-W60G β2m mutant, where a Pro residue has been introduced in the type I β-turn i + 1 position. The K58P-W60G mutant shows improved chemical and temperature stability and faster folding relative to wt β2m. The crystal structure (1.25 ? resolution) shows that the Cys25-Cys80 disulphide bridge is unexpectedly severed, in agreement with electrospray ionization-mass spectrometry (ESI-MS) spectra that indicate that a fraction of the purified protein lacks the internal disulphide bond. These observations suggest a stabilizing role for Pro58, and stress a crucial role for the DE loop in determining β2m biophysical properties. 相似文献
54.
Giorgetti S Raimondi S Pagano K Relini A Bucciantini M Corazza A Fogolari F Codutti L Salmona M Mangione P Colombo L De Luigi A Porcari R Gliozzi A Stefani M Esposito G Bellotti V Stoppini M 《The Journal of biological chemistry》2011,286(3):2121-2131
The discovery of methods suitable for the conversion in vitro of native proteins into amyloid fibrils has shed light on the molecular basis of amyloidosis and has provided fundamental tools for drug discovery. We have studied the capacity of a small library of tetracycline analogues to modulate the formation or destructuration of β2-microglobulin fibrils. The inhibition of fibrillogenesis of the wild type protein was first established in the presence of 20% trifluoroethanol and confirmed under a more physiologic environment including heparin and collagen. The latter conditions were also used to study the highly amyloidogenic variant, P32G. The NMR analysis showed that doxycycline inhibits β2-microglobulin self-association and stabilizes the native-like species through fast exchange interactions involving specific regions of the protein. Cell viability assays demonstrated that the drug abolishes the natural cytotoxic activity of soluble β2-microglobulin, further strengthening a possible in vivo therapeutic exploitation of this drug. Doxycycline can disassemble preformed fibrils, but the IC(50) is 5-fold higher than that necessary for the inhibition of fibrillogenesis. Fibril destructuration is a dynamic and time-dependent process characterized by the early formation of cytotoxic protein aggregates that, in a few hours, convert into non-toxic insoluble material. The efficacy of doxycycline as a drug against dialysis-related amyloidosis would benefit from the ability of the drug to accumulate just in the skeletal system where amyloid is formed. In these tissues, the doxycycline concentration reaches values several folds higher than those resulting in inhibition of amyloidogenesis and amyloid destructuration in vitro. 相似文献
55.
Raimondi E Piras FM Nergadze SG Di Meo GP Ruiz-Herrera A Ponsà M Ianuzzi L Giulotto E 《Hereditas》2011,148(3):110-113
In the karyotype of Equus asinus (domestic donkey, 2n = 62), non-centromeric heterochromatic bands have been described in subcentromeric and telomeric positions. In particular, chromosome 1 is characterised by heterochromatic bands in the proximal region of the long arm and in the short arm; it has been shown that these regions are polymorphic in size. Here we investigated the variation in the intensity and distribution of fluorescence signals observed on donkey chromosome 1 after in situ hybridization with two DNA probes containing fragments from the two major equine satellite DNA families. Our results show that, in Equus asinus chromosome 1, the amount and distribution of large clusters of satellite DNA can define at least nine polymorphic variants of the constitutive heterochromatin that cannot be detected by C-banding alone. 相似文献
56.
Balestrazzi A Agoni V Tava A Avato P Biazzi E Raimondi E Macovei A Carbonera D 《Physiologia plantarum》2011,141(3):227-238
The present work reports on the biological activity of alfalfa (Medicago sativa) saponins on white poplar (Populus alba, cultivar ‘Villafranca’) cell suspension cultures. The extracts from alfalfa roots, aerial parts and seeds were characterized for their saponin content by means of thin layer chromatography (TLC) and electrospray ionisation coupled to mass spectrometry. The quantitative saponin composition from the different plant extracts was determined considering the aglycone moieties and determined by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) analyses. Only soyasapogenin I was detected in the seed extract while several other saponins were found in the root and leaf extracts. Actively proliferating white poplar cell cultures were challenged with the different saponin extracts. Only alfalfa root saponins, at 50 µg ml?1, induced significant cell death rates (75.00 ± 4.90%). Different cell subpopulations with peculiar cell death morphologies were observed and the programmed cell death (PCD)/necrosis ratio was reduced at increasing saponin concentrations. Enhancement of nitric oxide (NO) production was observed in white poplar cells treated with root saponins (RSs) at 50 µg ml?1 and release of reactive oxygen species (ROS) in the culture medium was also demonstrated. Saponin‐induced NO production was sensitive to sodium azide and NG‐monomethyl‐l ‐arginine, two specific inhibitors of distinct pathways for NO biosynthesis in plant cells. 相似文献
57.
Roncaglia L Amaretti A Raimondi S Leonardi A Rossi M 《Applied microbiology and biotechnology》2011,92(1):159-168
Lignans are ubiquitous plant polyphenols, which have relevant health properties being the major phytoestrogens occurring in
Western diets. Secoisolariciresinol (SECO) is the major dietary lignan mostly found in plants as secoisolariciresinol diglucoside
(SDG). To exert biological activity, SDG requires being deglycosylated to SECO and transformed to enterodiol (ED) and enterolactone
(EL) by the intestinal microbes. The involvement of bifidobacteria in the transformation of lignans glucosides has been investigated
for the first time in this study. Twenty-eight strains were assayed for SDG and SECO activation. They all failed to transform
SECO into reduced metabolites, excluding any role in ED and EL production. Ten Bifidobacterium cultures partially hydrolyzed SDG, giving both SECO and the monoglucoside with yields < 25%. When the cell-free extracts
were assayed in SDG transformation, seven additional strains were active in the hydrolysis. Cellobiose induced β-glucosidase
activity and caused the enhancement of both the rate of SDG hydrolysis and the final yield of SECO only in the strains capable
of SDG bioconversion. The highest SDG conversion to SECO was achieved by Bifidobacterium pseudocatenulatum WC 401, which exhibited 75% yield in cellobiose-based medium after 48 h. These results indicate that SDG hydrolysis is not
a common feature in Bifidobacterium genus, but selected probiotic strains can be combined to β-glucoside-based prebiotics to enhance the release of SECO, thus
improving its bioavailability for absorption by colonic mucosa and/or the biotransformation to ED and EL by other intestinal
microorganisms. 相似文献
58.
Laura Milazzo Anna Maria Peri Cristina Mazzali Romualdo Grande Chiara Cazzani Davide Ricaboni Antonio Castelli Ferdinando Raimondi Carlo Magni Massimo Galli Spinello Antinori 《Mycopathologia》2014,178(3-4):227-241
Background
Candida species represent the fourth leading cause of nosocomial bloodstream infections (BSI) worldwide. However, candidaemia rates and species involved vary geographically.Objectives
To evaluate the epidemiological pattern, risk factors for mortality and antifungal therapy of Candida BSI over a 5-year period (2008–2012) in a university hospital in northern Italy together with a review of the recent literature concerning candidaemia.Methods
A retrospective cohort study cross-linked with microbiology database was performed.Results
A total of 89 Candida BSI were identified in 42 males (47 %) and 47 females (52.8 %). The median age was 69 years (interquartile range 55–78) with 61.8 % of patients being older than 65 years. Considering all hospitalized patients, the overall incidence rate of candidaemia increased significantly from 2008 to 2012 (from 0.4 to 1.68 episodes per 10,000 patient/days) (p = 0.0001) with a mean linear increase in 5 new cases per year. Candida albicans was the predominant species isolated (64 %) followed by C. glabrata (19.1 %). The latter species was observed with significantly higher frequency in Internal Medicine and Intensive Care Units (ICU). In-hospital crude mortality was 41.6 %.Conclusions
Candidaemia is an increasing BSI in our university hospital, in accordance with that observed in northern Italy, and it is still associated with high in-hospital crude mortality. 相似文献59.
Sarah K. Knutson Natalie M. Warholic L. Danielle Johnston Christine R. Klaus Tim J. Wigle Dorothy Iwanowicz Bruce A. Littlefield Margaret Porter-Scott Jesse J. Smith Mikel P. Moyer Robert A. Copeland Roy M. Pollock Kevin W. Kuntz Alejandra Raimondi Heike Keilhack 《PloS one》2014,9(12)
Patients with non-Hodgkin lymphoma (NHL) are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone). Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone – a glucocorticoid receptor agonist (GRag) component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting. 相似文献