全文获取类型
收费全文 | 2264篇 |
免费 | 156篇 |
出版年
2023年 | 4篇 |
2022年 | 25篇 |
2021年 | 30篇 |
2020年 | 16篇 |
2019年 | 33篇 |
2018年 | 60篇 |
2017年 | 43篇 |
2016年 | 81篇 |
2015年 | 114篇 |
2014年 | 98篇 |
2013年 | 161篇 |
2012年 | 199篇 |
2011年 | 192篇 |
2010年 | 121篇 |
2009年 | 112篇 |
2008年 | 150篇 |
2007年 | 130篇 |
2006年 | 109篇 |
2005年 | 111篇 |
2004年 | 122篇 |
2003年 | 103篇 |
2002年 | 121篇 |
2001年 | 13篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 22篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 15篇 |
1994年 | 13篇 |
1993年 | 18篇 |
1992年 | 18篇 |
1991年 | 13篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 11篇 |
1981年 | 11篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1975年 | 11篇 |
1974年 | 7篇 |
1963年 | 2篇 |
排序方式: 共有2420条查询结果,搜索用时 21 毫秒
181.
Mario Melletti M. M. Delgado Vincenzo Penteriani Marzia Mirabile Luigi Boitani 《Journal of Ethology》2010,28(3):421-428
Many animals aggregate into organized temporary or stable groups under the influence of biotic and abiotic factors, and some
studies have shown the influence of habitat features on animal aggregation. This study, conducted from 2002 to 2004 in the
Dzanga-Ndoki National Park, Central African Republic, studied a herd of forest buffaloes (Syncerus caffer nanus) to determine whether spatial aggregation patterns varied by season and habitat. Our results show that both habitat structure
and season influenced spatial aggregation patterns. In particular, in open habitats such as clearings, the group covered a
larger area when resting and was more rounded in shape compared to group properties noted in forest during the wet season.
Moreover, forest buffaloes had a more aggregated spatial distribution when resting in clearings than when in the forest, and
individual positions within the herd in the clearing habitat varied with age and sex. In the clearings, the adult male (n = 24) was generally, on most occasions, located in the centre of the herd (n = 20), and he was observed at the border only four times. In contrast, females (n = 80) occupied intermediate (n = 57), peripheral (n = 14) and central positions (n = 9) within the group. Juveniles (n = 77) also occurred in intermediate (n = 64) and peripheral positions (n = 13). Based on these results, we concluded that habitat characteristics and social behaviour can have relevant effects on
the spatial distribution of animals within a group. 相似文献
182.
Stefano Lancellotti Vincenzo De Filippis Nicola Pozzi Flora Peyvandi Roberta Palla Bianca Rocca Sergio Rutella Dario Pitocco Pier Mannuccio Mannucci Raimondo De Cristofaro 《Free radical biology & medicine》2010,48(3):446-456
An enhanced formation of reactive oxygen species and peroxynitrite occurs in several clinical settings including diabetes, coronary artery disease, stroke, sepsis, and chronic inflammatory diseases. Peroxynitrite oxidizes methionine and tyrosine residues to methionine sulfoxide (MetSO) and 3-nitrotyrosine (NT), respectively. Notably, ADAMTS-13 cleaves von Willebrand factor (VWF) exclusively at the Tyr1605–Met1606 peptide bond in the A2 domain. We hypothesized that peroxynitrite could oxidize either or both of these amino acid residues, thus potentially affecting ADAMTS-13-mediated cleavage. We tested our hypothesis using synthetic peptide substrates based on: (1) VWF Asp1596–Ala1669 sequence (VWF74) and (2) VWF Asp1596–Ala1669 sequence containing nitrotyrosine (VWF74-NT) or methionine sulfoxide (VWF74-MetSO) at position 1605 or 1606, respectively. The peptides were treated with recombinant ADAMTS-13 and the cleavage products analyzed by RP-HPLC. VWF74 oxidized by peroxynitrite underwent a severe impairment of its hydrolysis. Likewise, VWF74-MetSO was minimally hydrolyzed, whereas VWF74-NT was hydrolyzed slightly more efficiently than VWF74. Oxidation by peroxynitrite of purified VWF multimers inhibited ADAMTS-13 hydrolysis, but did not alter their electrophoretic pattern nor their ability to induce platelet agglutination by ristocetin. Moreover, VWF purified from type 2 diabetic patients showed oxidative damage, as revealed by enhanced carbonyl, NT, and MetSO content and was partially resistant to ADAMTS-13 hydrolysis. In conclusion, peroxynitrite may contribute to prothrombotic effects, hindering the proteolytic processing by ADAMTS-13 of high-molecular-weight VWF multimers, which have the highest ability to bind and activate platelets in the microcirculation. 相似文献
183.
Longevity and age at sexual maturity were estimated in two anurans from the arid Isalo Massif (southern-central Madagascar), the blue-legged frog (Mantella expectata) and the rainbow frog (Scaphiophryne gottlebei). Phalanges from 69 individuals of M. expectata and 38 individuals of S. gottlebei were analyzed, using the skeletochronological method, in samples collected during two periods: January-February and November-December 2004. The male gonads of both species were also analyzed in order to better correlate reproductive activity with phenology. The phalangeal diaphysis in adults of both species was composed of two concentric bone layers: an innermost endosteal bone, which was less developed or sometimes lacking in S. gottlebei, and an outermost and broader layer of periosteal bone. Lines of arrested growth (LAGs) were observed in both species, although their recognition was more problematic and their distinctiveness much less evident in S. gottlebei. The results presented here indicate that M. expectata and S. gottlebei have a short life span and attain sexual maturity within the first active season after metamorphosis. Maximum longevity was 3 years in M. expectata and 2 years in S. gottlebei. In S. gottlebei the adult body size is likely attained during the same season in which metamorphosis occurs, but then breeding occurs only after the first latency period. Thus, mature individuals have only one LAG, corresponding to 1 year. The low number of individuals with two LAGs suggests that most animals die before the second latency period. 相似文献
184.
Margherita Sisto Sabrina Lisi Dario Domenico Lofrumento Giuseppe Ingravallo Vincenzo Mitolo Massimo D’Amore 《Histochemistry and cell biology》2010,134(4):345-353
The tumor-necrosis-factor-converting-enzyme (TACE)-TNF-α-Amphiregulin (AREG) axis plays an important pathogenic role in inflammatory and autoimmune disorders. However, the pathological roles of these proteins in the chronic autoimmune disease Sjögren’s syndrome (SS) remain to be elucidated. It is known that the TACE–AREG axis is clearly part of a larger cascade of signals that starts with the activation of Furin, responsible for maturation of TACE that, in turn, determines the production of active TNF-α, directly involved in the up-regulation of AREG expression. This study showed that Furin, TACE, TNF-α, and AREG proteins, detected in acinar and ductal cells of human salivary glands from SS patients, increased remarkably in comparison with biopsies of labial salivary glands from healthy controls. The changes in Furin, TACE, TNF- α, and AREG proteins’ level detected in salivary glands biopsies of SS patients could be responsible for pro-inflammatory cytokines overexpression characterizing Sjögren’s syndrome. 相似文献
185.
Rafael Torres Martin de Rosales Marina Faiella Erik Farquhar Lawrence Que Jr Concetta Andreozzi Vincenzo Pavone Ornella Maglio Flavia Nastri Angela Lombardi 《Journal of biological inorganic chemistry》2010,15(5):717-728
The design, synthesis, and metal-binding properties of DF3, a new de novo designed di-iron protein model are described (“DF”
represents due ferri, Italian for “two iron,” “di-iron”). DF3 is the latest member of the DF family of synthetic proteins. They consist of helix–loop–helix
hairpins, designed to dimerize and form an antiparallel four-helix bundle that encompasses a metal-binding site similar to
those of non-heme carboxylate-bridged di-iron proteins. Unlike previous DF proteins, DF3 is highly soluble in water (up to
3 mM) and forms stable complexes with several metal ions (Zn, Co, and Mn), with the desired secondary structure and the expected
stoichiometry of two ions per protein. UV–vis studies of Co(II) and Fe(III) complexes confirm a metal-binding environment
similar to previous di-Co(II)- and di-Fe(III)-DF proteins, including the presence of a μ-oxo-di-Fe(III) unit. Interestingly,
UV–vis, EPR, and resonance Raman studies suggest the interaction of a tyrosine adjacent to the di-Fe(III) center. The design
of DF3 was aimed at increasing the accessibility of small molecules to the active site of the four-helix bundle. Indeed, binding
of azide to the di-Fe(III) site demonstrates a more accessible metal site compared with previous DFs. In fact, fitting of
the binding curve to the Hill equation allows us to quantify a 150% accessibility enhancement, with respect to DF2. All these
results represent a significant step towards the development of a functional synthetic DF metalloprotein. 相似文献
186.
Houman Ashrafian Louise Docherty Vincenzo Leo Christopher Towlson Monica Neilan Violetta Steeples Craig A. Lygate Tertius Hough Stuart Townsend Debbie Williams Sara Wells Dominic Norris Sarah Glyn-Jones John Land Ivana Barbaric Zuzanne Lalanne Paul Denny Dorota Szumska Shoumo Bhattacharya Julian L. Griffin Iain Hargreaves Narcis Fernandez-Fuentes Michael Cheeseman Hugh Watkins T. Neil Dear 《PLoS genetics》2010,6(6)
Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease. 相似文献
187.
Vincenzo Giannini Rogelio Rodríguez-Oliveros Jose A. Sánchez-Gil 《Plasmonics (Norwell, Mass.)》2010,5(1):99-104
We investigate theoretically the optical properties associated to plasmon resonances of metal nanowires with cross section
given by low-order Chebyshev nanoparticles (like rounded-tip nanostars or nanoflowers). The impact of the nanoflower shape
is analyzed for varying symmetry and deformation parameter through the spectral dependence of resonances and their corresponding
near field distributions. Large field intensity enhancements are obtained at the gaps between petals, apart from the tips
themselves, which make these nanostars/nanoflowers specially suitable to host molecules for surface-enhanced Raman scattering
sensing applications. 相似文献
188.
Roberta Biasiotto Paola Aguiari Rosario Rizzuto Paolo Pinton Donna M. D'Agostino Vincenzo Ciminale 《BBA》2010,1797(6-7):945-951
Human T cell leukemia virus type 1 (HTLV-1) encodes p13, an 87-amino-acid protein that accumulates in the inner mitochondrial membrane. Recent studies performed using synthetic p13 and isolated mitochondria demonstrated that the protein triggers an inward potassium (K+) current and inner membrane depolarization. The present study investigated the effects of p13 on mitochondrial inner membrane potential (Δψ) in living cells. Using the potential-dependent probe tetramethyl rhodamine methyl ester (TMRM), we observed that p13 induced dose-dependent mitochondrial depolarization in HeLa cells. This effect was abolished upon mutation of 4 arginines in p13's α-helical domain that were previously shown to be essential for its activity in in vitro assays. As Δψ is known to control mitochondrial calcium (Ca2+) uptake, we next analyzed the effect of p13 on Ca2+ homeostasis. Experiments carried out in HeLa cells expressing p13 and organelle-targeted aequorins revealed that the protein specifically reduced mitochondrial Ca2+ uptake. These observations suggest that p13 might control key processes regulated through Ca2+ signaling such as activation and death of T cells, the major targets of HTLV-1 infection. 相似文献
189.
Luca Vitale Paul Di Tommasi Carmen Arena Angelo Fierro Amalia Virzo De Santo Vincenzo Magliulo 《Acta Physiologiae Plantarum》2007,29(4):317-326
Zea mays is cultivated in the Mediterranean regions where summer drought may lead to photoinhibition when irrigation is not available.
In this work the response of maize to water stress was evaluated by gas exchange measurements at the canopy and leaf level.
Leaf gas exchange was assessed before, during and after water stress, while canopy turbulent fluxes of mass and energy were
performed on a continuous basis. In the early growth period, a linear increment of net ecosystem photosynthetic rate (P
NE) to incoming of photosynthetic photon flux density (PPFD) was found and net leaf photosynthetic rate (P
NL) showed the tendency to saturate under high irradiance. During water stress, the relationship between P
NE and PPFD became curvilinear and both P
NE and P
NL saturated in a range between 1,000 and 1,500 μmol (photons) m−2 s−1. Leaf water potential (ψl) dropped from −1.50 to −1.88 MPa during water stress, indicating that leaf and canopy gas exchanges were limited by stomatal
conductance. With the restoration of irrigation, P
NE, P
NL and ψl showed a recovery, and P
NE and P
NL reached the highest values of whole study period. Leaf area index (LAI) reached a value of 3.0 m2 m−2. The relationship between P
NE and PPFD remained curvilinear and P
NE values were lower than those of a typical well-irrigated maize crop. The recovery in P
NE and P
NL after stress, and ψl values during stress indicate that the photosynthetic apparatus was not damaged while soil moisture stress after-effects
resulted in a sub-optimal LAI values, which in turn depressed P
NE. 相似文献
190.
Expression of deacetylvindoline-4-O-acetyltransferase in Catharanthus roseus hairy roots 总被引:3,自引:0,他引:3
Madagascar periwinkle [Catharanthus roseus (L.) G Don] is a pantropical plant of horticultural value that produces the powerful anticancer drugs vinblastine and vincristine that are derived from the dimerization of the monoterpenoid indole alkaloids (MIAs), vindoline and catharanthine. The present study describes the genetic engineering and expression of the terminal step of vindoline biosynthesis, deacetylvindoline-4-O-acetyltransferase (DAT) in Catharanthus roseus hairy root cultures. Biochemical analyses showed that several hairy root lines expressed high levels of DAT enzyme activity compared to control hairy root cultures expressing β-gulucuronidase activity (GUS) activity. Metabolite analysis using high performance liquid chromotagraphy established that hairy root extracts had an altered alkaloid profile with respect to hörhammericine accumulation in DAT expressing lines in comparison to control lines. Further analyses of one hairy root culture expressing high DAT activity suggested that DAT expression and accumulation of hörhammericine (9) were related. It is concluded that expression of DAT in hairy roots altered their MIA profile and suggests that further expression of vindoline pathway genes could lead to significant changes in alkaloid profiles. Evidence is provided that hörhammericine (9) accumulates via a DAT interaction with the root specific minovincinine-19-O-acetyltransferase (MAT) that inhibits the MAT mediated conversion of hörhammericine (9) into 19-O-acetyl-hörhammericine (12). 相似文献