全文获取类型
收费全文 | 739篇 |
免费 | 78篇 |
出版年
2024年 | 1篇 |
2023年 | 8篇 |
2022年 | 11篇 |
2021年 | 20篇 |
2020年 | 15篇 |
2019年 | 12篇 |
2018年 | 21篇 |
2017年 | 21篇 |
2016年 | 25篇 |
2015年 | 49篇 |
2014年 | 44篇 |
2013年 | 54篇 |
2012年 | 82篇 |
2011年 | 65篇 |
2010年 | 33篇 |
2009年 | 32篇 |
2008年 | 31篇 |
2007年 | 51篇 |
2006年 | 56篇 |
2005年 | 26篇 |
2004年 | 32篇 |
2003年 | 20篇 |
2002年 | 26篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 12篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 7篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 2篇 |
排序方式: 共有817条查询结果,搜索用时 15 毫秒
1.
A Poletti F Celotti R C Melcangi M Ballabio L Martini 《Journal of steroid biochemistry》1990,35(1):97-101
The 5 alpha-reductase, the enzyme which converts testosterone into dihydrotestosterone (DHT), is present in several CNS structures of the rat. Recent reports from this laboratory indicate that the subcortical white matter and the myelin possess a 5 alpha-reductase activity several times higher than that present in the cerebral cortex. Moreover, previous ontogenetic observations indicate that in all cerebral tissues examined (including the myelin) the 5 alpha-reductase has a higher activity in immature animals. This study was performed in order to verify whether the differences in the 5 alpha-reductase activity on the various brain components might be due to the presence of different concentrations of the same enzyme or to different isoenzymes. To this purpose, the kinetic properties Km and Vmax were measured in the purified myelin as well as in homogenates of the subcortical white matter and of the cerebral cortex, obtained from the brain of adult (60-90-day-old), immature (23-day-old), and aged (greater than 20-month-old) male rats. The results indicate that the enzymes present in the myelin, in the subcortical white matter and in the cerebral cortex of adult male rats possess a very similar apparent Km (1.93 +/- 0.2, 2.72 +/- 0.73 and 3.83 +/- 0.49 microM respectively). On the contrary, the Vmax values obtained in the myelin (34.40 +/- 5.54), in the white matter (19.57 +/- 2.36) and in the cerebral cortex (6.47 +/- 1.03 ng/h/mg protein) of adult animals have been found to be consistently different. Very similar Km values were found in the myelin obtained from the brain of immature and very old rats (2.14 +/- 0.11 and 3.39 +/- 0.75 microM respectively). The Vmax measured in the myelin purified from the immature rat brain (62.25 +/- 4.52) showed a value which was much higher than that found in the myelin of adult animals (34.40 +/- 5.54); a Vmax (34.31 +/- 9.41) almost identical to that of adult animals was found in the myelin prepared from the brain of aged rats. 相似文献
2.
X-linked Alport syndrome: an SSCP-based mutation survey over all 51 exons of the COL4A5 gene. 总被引:13,自引:1,他引:12
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A. Renieri M. Bruttini L. Galli P. Zanelli T. Neri S. Rossetti A. Turco N. Heiskari J. Zhou R. Gusmano L. Massella G. Banfi F. Scolari A. Sessa G. Rizzoni K. Tryggvason P. F. Pignatti M. Savi A. Ballabio M. De Marchi 《American journal of human genetics》1996,58(6):1192-1204
The COL4A5 gene encodes the alpha5 (type IV) collagen chain and is defective in X-linked Alport syndrome (AS). Here, we report the first systematic analysis of all 51 exons of COL4A5 gene in a series of 201 Italian AS patients. We have previously reported nine major rearrangements, as well as 18 small mutations identified in the same patient series by SSCP analysis of several exons. After systematic analysis of all 51 exons of COL4A5, we have now identified 30 different mutations: 10 glycine substitutions in the triple helical domain of the protein, 9 frameshift mutations, 4 in-frame deletions, 1 start codon, 1 nonsense, and 5 splice-site mutations. These mutations were either unique or found in two unrelated families, thus excluding the presence of a common mutation in the coding part of the gene. Overall, mutations were detected in only 45% of individuals with a certain or likely diagnosis of X-linked AS. This finding suggests that mutations in noncoding segments of COL4A5 account for a high number of X-linked AS cases. An alternative hypothesis is the presence of locus heterogeneity, even within the X-linked form of the disease. A genotype/phenotype comparison enabled us to better substantiate a significant correlation between the degree of predicted disruption of the alpha5 chain and the severity of phenotype in affected male individuals. Our study has significant implications in the diagnosis and follow-up of AS patients. 相似文献
3.
Nadia Mastroianni Maurizio De Fusco Massimo Zollo Giulia Arrigo Orsetta Zuffardi Alberto Bettinelli Andrea Ballabio Giorgio Casari 《Genomics》1996,35(3):486
Electrolyte homeostasis is maintained by several ion transport systems. Na–(K)–Cl cotransporters promote the electrically silent movement of chloride across the membrane in absorptive and secretory epithelia. Two kidney-specific Na–(K)–Cl cotransporter isoforms are known, so far, according to their sensitivity to specific inhibitors. We have cloned the human cDNA coding for the renal Na–Cl cotransporter selectively inhibited by the thiazide class of diuretic agents. The predicted protein sequence of 1021 amino acids (112 kDa) shows a structure common to the other members of the Na–(K)–Cl cotransporter family: a central region harboring 12 transmembrane domains and the 2 intracellular hydrophilic amino and carboxyl termini. The ex- pression pattern of the human Na–Cl thiazide-sensitive cotransporter (hTSC, HGMW-approved symbol SLC12A3) confirms the kidney specificity. hTSC has been mapped to human chromosome 16q13 by fluorescencein situhybridization. The cloning and characterization of hTSC now render it possible to study the involvement of this cotransport system in the pathogenesis of tubulopathies such as Gitelman syndrome. 相似文献
4.
Neuza Domingues André R. A. Marques Rita Diogo Almeida Calado Inês S. Ferreira Cristiano Ramos José Ramalho Maria I. L. Soares Telmo Pereira Luís Oliveira José R. Vicente Louise H. Wong Inês C. M. Simões Teresa M. V. D. Pinho e Melo Andrew Peden Cláudia Guimas Almeida Clare E. Futter Rosa Puertollano Winchil L. C. Vaz Otília V. Vieira 《Traffic (Copenhagen, Denmark)》2023,24(7):284-307
5.
Papillomavirus capsid binding and uptake by cells from different tissues and species. 总被引:22,自引:14,他引:8
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M Müller L Gissmann R J Cristiano X Y Sun I H Frazer A B Jenson A Alonso H Zentgraf J Zhou 《Journal of virology》1995,69(2):948-954
The inability of papillomaviruses (PV) to replicate in tissue culture cells has hampered the study of the PV life cycle. We investigated virus-cell interactions by the following two methods: (i) using purified bovine PV virions or human PV type 11 (HPV type 11) virus-like particles (VLP) to test the binding to eukaryotic cells and (ii) using different VLP-reporter plasmid complexes of HPV6b, HPV11 L1 or HPV11 L1/L2, and HPV16 L1 or HPV16 L1/L2 to study uptake of particles into different cell lines. Our studies showed that PV capsids bind to a broad range of cells in culture in a dose-dependent manner. Binding of PV capsids to cells can be blocked by pretreating the cells with the protease trypsin. Penetration of PV into cells was monitored by using complexes in which the purified PV capsids were physically linked to DNA containing the gene for beta-galactosidase driven by the human cytomegalovirus promoter. Expression of beta-galactosidase occurred in < 1% of the cells, and the efficiency of PV receptor-mediated gene delivery was greatly enhanced (up to 10 to 20% positive cells) by the use of a replication-defective adenovirus which promotes endosomal lysis. The data generated by this approach further confirmed the results obtained from the binding assays, showing that PV enter a wide range of cells and that these cells have all functions required for the uptake of PV. Binding and uptake of PV particles can be blocked by PV-specific antisera, and different PV particles compete for particle uptake. Our results suggest that the PV receptor is a conserved cell surface molecule(s) used by different PV and that the tropism of infection by different PV is controlled by events downstream of the initial binding and uptake. 相似文献
6.
Regulation by estrogen through the 5'-flanking region of the transforming growth factor alpha gene. 总被引:2,自引:0,他引:2
T Saeki A Cristiano M J Lynch M Brattain N Kim N Normanno N Kenney F Ciardiello D S Salomon 《Molecular endocrinology (Baltimore, Md.)》1991,5(12):1955-1963
Expression of transforming growth factor alpha (TGF alpha) mRNA and protein can be stimulated by estrogens such as 17 beta-estradiol (E2) in estrogen-responsive rodent and human breast cancer cells. To ascertain if E2 can directly regulate TGF alpha expression through the 5'-flanking region of the human TGF alpha gene, E2-responsive MCF-7 or ZR-75-1 human breast cancer cells or E2-nonresponsive MDA-MB-231 breast cancer cells were transiently transfected with a plasmid containing an 1140-base pair (bp) Sac-I fragment of the TGF alpha 5'-flanking region ligated to the chloramphenicol acetyltransferase (CAT) gene. Cells that were transfected and subsequently treated with physiological concentrations of E2 (10(-11)-10(-8) M) for 24 h exhibited a 2- to 10-fold increase in CAT activity. The E2 stimulation of CAT activity was dose-dependent with an increase first found at 10(-10) M E2. The increase in CAT activity could be detected within 24-36 h after the addition of E2. There was no significant change in CAT activity in transiently transfected MDA-MB-231 cells as mediated through the TGF alpha 5'-flanking region after E2 treatment. MCF-7 cells were also transiently transfected with different fragments of the TGF alpha 5'-flanking region ligated to the luciferase gene. In the absence of E2 treatment, no detectable luciferase activity was found.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
7.
Cristiano Carlomagno Monia Cabinio Silvia Picciolini Alice Gualerzi Francesca Baglio Marzia Bedoni 《Journal of biophotonics》2020,13(3)
Alzheimer disease (AD) is the most common form of dementia in the elderly, progressively affecting the cognitive functions with a complex diagnostic procedure that limits the time for a prompt intervention. In this study we optimized a reliable protocol for the analysis of AD patients and healthy subjects' serum using the Surface Enhanced Raman Spectroscopy (SERS), taking into consideration the effect of different variables on the final spectra, analyzed and compared through multivariate analysis and correlated with hippocampus volume. As results, we demonstrated a statistical difference between the spectra collected from the two investigated groups, with an accuracy, precision and specificity of respectively 83%, 86%, and 86%. The correlation of these data with those obtained from MRI, demonstrated a direct correlation between Raman spectra and hippocampus degeneration showing the Raman Spectroscopy (RS) as a potential tool for the monitoring of AD progression and rehabilitation treatments. 相似文献
8.
Cristiano Viappiani 《Biophysical chemistry》1994,50(3):293-304
In this work a combined pulsed-laser, time-resolved photoacoustic calorimetry (PAC) and fluorescence study is presented on two widely used covalent protein probes, fluorescein-5-isothiocyanate (FITC) and 6-acryloyl-2-dimethylaminonaphtalene (acrylodan). Three proteins that contain a single free thiol, namely carbonic anhydrase, bovine serum albumin (BSA) and papain, have been selectively labelled with FITC and acrylodan, and their fluorescence emission was quenched with KI. Nonradiative decays of the excited states of FITC are used to complement the information usually obtained by monitoring the quenching of fluorescence emssion. Data analysis evidences the dependence of the nonradiative quenching constants on the exposure of the dye to the solvent, and shows the involvement of a triplet state of FITC in the non radiative deexcitation. The shielding of the binding sites from the solvent is demonstrated also by the fluorescence emission of acrylodan and by the Stern-Volmer analysis of fluorescence quenching by KI. From photoacoustic data, an estimate of the fluorescent quantum yield of bound FITC is obtained. This work demonstrates the complete equivalence of quenching data obtained by fluorescence and photoacoustics measurements and shows that this combined approach allows a better control of the photophysics of the dyes involved in the quenching process. 相似文献
9.
Cristiano Nogueira Síria Ribeiro Gabriel C. Costa Guarino R. Colli 《Journal of Biogeography》2011,38(10):1907-1922
Aim To test predictions of the vicariance model, to define basic biogeographical units for Cerrado squamates, and to discuss previous biogeographical hypotheses. Location Cerrado; South American savannas south of the Amazon, extending across central Brazil, with marginal areas in Bolivia and Paraguay and isolated relictual enclaves in adjacent regions. Methods We compiled species occurrence records via field sampling and revision of museum specimens and taxonomic literature. All species were mapped according to georeferenced locality records, and classified as (1) endemic or non‐endemic, (2) typical of plateaus or depressions, and (3) typical of open or forested habitats. We tested predictions of the vicariance model using biotic element analysis, searching for non‐random clusters of species ranges. Spatial congruence of biotic elements was compared with putative areas of endemism revealed by sympatric restricted‐range species. Effects of topographical and vegetational mosaics on distribution patterns were studied according to species composition in biotic elements and areas of endemism. Results We recorded 267 Cerrado squamates, of which 103 (39%) are endemics, including 20 amphisbaenians (61% endemism), 32 lizards (42%) and 51 snakes (32%). Distribution patterns corroborated predictions of the vicariance model, revealing groups of species with significantly clustered ranges. An analysis of endemic species recovered seven biotic elements, corroborating results including non‐endemics. Sympatric restricted‐range taxa delimited 10 putative areas of endemism, largely coincident with core areas of biotic elements detected with endemic taxa. Distribution patterns were associated with major topographical and vegetational divisions of the Cerrado. Endemism prevailed in open, elevated plateaus, whereas faunal interchange, mostly associated with forest habitats, was more common in peripheral depressions. Main conclusions Our results indicate that vicariant speciation has strongly shaped Cerrado squamate diversity, in contrast to earlier studies emphasizing faunal interchange and low endemism in the Cerrado vertebrate fauna. Levels of squamate endemism are higher than in any other Cerrado vertebrate group. The high number of recovered endemics revealed previously undetected areas of evolutionary relevance, indicating that biogeographical patterns in the Cerrado were poorly represented in previous analyses. Although still largely undocumented, effects of vicariant speciation may be prevalent in a large fraction of Cerrado and Neotropical biodiversity. 相似文献
10.
Barbara Maichak de Carvalho Alejandra Vanina Volpedo Cristiano Queiroz Albuquerque Luís Fernando Fvaro 《Zeitschrift fur angewandte Ichthyologie》2019,35(6):1286-1291
Sagitta otoliths are usually formed of calcium carbonate polymorphs as aragonite. The objective of this study was to verify which carbonate polymorph is predominant in the sagitta otolith of Menticirrhus americanus and check whether this pattern remains in otoliths with morphological alterations. Otoliths of M. americanus were obtained from five sites on the southeast‐south coast of Brazil (São Sebastião (SS) 23°45′S–45°24′O, n = 29; Cananéia‐Iguape Estuarine Complex (CI) 25°02′S–47°54′O, n = 30; Paranaguá Estuarine Complex (PEC) 25°28′S–48°20′O, n = 35; Itapoá (IT) 26°07′S–48°36′O, n = 31; Laguna (LA) 28°28′S–48°46′O, n = 13). The characterization of carbonate polymorphs of otoliths was performed through Raman spectroscopy, a photonic and non‐destructive technique that analyzes molecular vibrations induced by laser. We analyzed 138 pairs of M. americanus otoliths, of which eight otoliths from different pairs presented morphological alterations (SS n = 1, CEP n = 5, IT n = 1, LA n = 1). The Raman spectra show that normal otoliths, that is, without morphological alterations, presented only aragonite in their structure. Among the otoliths that presented morphological alterations, the Raman spectra allowed to identify in six otoliths the deposition of aragonite and in only two otoliths the deposition of vaterite (one specimen of the PEC and one of SS). 相似文献