全文获取类型
收费全文 | 6405篇 |
免费 | 472篇 |
国内免费 | 1篇 |
出版年
2023年 | 19篇 |
2022年 | 67篇 |
2021年 | 133篇 |
2020年 | 79篇 |
2019年 | 139篇 |
2018年 | 182篇 |
2017年 | 144篇 |
2016年 | 224篇 |
2015年 | 289篇 |
2014年 | 381篇 |
2013年 | 454篇 |
2012年 | 497篇 |
2011年 | 470篇 |
2010年 | 306篇 |
2009年 | 253篇 |
2008年 | 380篇 |
2007年 | 348篇 |
2006年 | 291篇 |
2005年 | 296篇 |
2004年 | 302篇 |
2003年 | 268篇 |
2002年 | 242篇 |
2001年 | 102篇 |
2000年 | 80篇 |
1999年 | 73篇 |
1998年 | 53篇 |
1997年 | 40篇 |
1996年 | 58篇 |
1995年 | 32篇 |
1994年 | 33篇 |
1993年 | 33篇 |
1992年 | 57篇 |
1991年 | 48篇 |
1990年 | 43篇 |
1989年 | 34篇 |
1988年 | 39篇 |
1987年 | 29篇 |
1986年 | 28篇 |
1985年 | 31篇 |
1984年 | 19篇 |
1983年 | 31篇 |
1982年 | 26篇 |
1981年 | 24篇 |
1980年 | 23篇 |
1979年 | 18篇 |
1977年 | 18篇 |
1976年 | 15篇 |
1975年 | 19篇 |
1974年 | 17篇 |
1972年 | 15篇 |
排序方式: 共有6878条查询结果,搜索用时 15 毫秒
991.
E Trujillo D Alvarez de la Rosa A Mobasheri T González C M Canessa P Martín-Vasallo 《Histology and histopathology》1999,14(4):1023-1031
In this article, the second of two, we continue our studies of sodium-dependent transport systems in human cartilage from healthy individuals and with osteoarthritis (OA) and rheumatoid arthritis (RA). We demonstrate the presence of the epithelial sodium channel (ENaC), previously undescribed in chondrocytes. This system is composed of three subunits, alpha, beta and gamma. We have shown that the human chondrocytes express at least the alpha and the beta subunit of ENaC. The expression of these subunits is altered in arthritic chondrocytes. In RA samples the quantity of alpha and beta is significantly higher than in control samples. On the other hand, ENaC alpha and beta subunits are absent in the chondrocytes of OA cartilage. Human chondrocytes also possess three isoforms of the Na+/H+ exchanger (NHE), NHE1, NHE2 and NHE3. The NHE system is composed of a single protein and is believed to participate in intracellular pH regulation. Furthermore, our studies indicate that at least one isoform of the electroneutral Na+/K+/2Cl- cotransporter (NKCC) is present in human chondrocytes. There are no obvious variations in the relative expression of NHE isoforms or NKCC between healthy and arthritic cartilage. Our data suggests that chondrocytes from arthritic cartilage may adapt to changes in their environmental sodium concentration through variations in ENaC protein levels. ENaC is also likely to serve as a major sodium entry mechanism, a process that, along with cytoskeletal proteins, may be part of mechanotransduction in cartilage. 相似文献
992.
Xavier Dolcet Joaquim Egea Rosa M. Soler Dionisio Martin-Zanca Joan X. Comella 《Journal of neurochemistry》1999,73(2):521-531
Chick embryo spinal cord motoneurons develop a trophic response to some neurotrophins when they are maintained in culture in the presence of muscle extract. Thus, after 2 days in culture, brain-derived neurotrophic factor (BDNF) promotes motoneuron survival. In the present study we have analyzed the intracellular pathways that may be involved in the BDNF-induced motoneuron survival. We have observed that BDNF activated the extracellular-regulated kinase (ERK) mitogen-activated protein (MAP) kinase and the phosphatidylinositol (PI) 3-kinase pathways. To examine the contribution of these pathways to the survival effect triggered by BDNF, we used PD 98059, a specific inhibitor of MAP kinase kinase, and LY 294002, a selective inhibitor of PI 3-kinase. PD 98059, at doses that significantly reduced the phosphorylation of ERKs, did not show any prominent effect on neuronal survival. However, LY 294002 at doses that inhibited the phosphorylation of Akt, a down-stream element of the PI 3-kinase, completely abolished the motoneuron survival effects of BDNF. Moreover, cell death triggered by LY 294002 treatment exhibited features similar to those observed after muscle extract deprivation. Our results suggest that the PI 3-kinase pathway plays an important role in the survival effect triggered by BDNF on motoneurons, whereas activation of the ERK MAP kinase pathway is not relevant. 相似文献
993.
Exploratory analysis of marked point patterns has previously been conducted using two disjoint techniques, namely the mark correlation function and spectral analysis. Our purpose here is to present two alternative autocovariance estimators to the mark correlation function which not only apply in both planar and lattice situations, but which in the lattice case can also be considered in terms of the inverse Fourier transform of the spectrum. Moreover, they can be applied to isotropic or anisotropic marked point patterns. Various examples are presented to show how these estimators perform when applied to data sets possessing different kinds of mark structure, and a rank test procedure is proposed to enable the construction of empirical tests of hypothesis. 相似文献
994.
L. F. B. P. Costa Rosa M. Kazantzis M. C. L. Seelaender 《Cell biochemistry and function》1998,16(3):195-202
The liver plays a central role in the establishment and maintenance of the cachectic state in rats bearing extra-hepatic tumours. Kupffer cells, which as macrophages, show a strong relationship between metabolism and function could be involved in the alterations observed in the disruption of many functions of the organ as a whole. To assess whether the metabolic/functional pattern of Kupffer cells was altered by cachexia we have investigated the utilization of glucose, glutamine and palmitate by the cells from tumour-bearing and control rats. We have found an enhanced utilization of the three substrates by the cells from tumour-bearing rats as compared with controls, which was related to greater energy production through the Krebs cycle and enhanced production of precursors for the synthesis of the many substances the cells secrete when activated. The use of palmitate as substrate was also augmented in these cells, in the opposition to the observation in stimulated peritoneal macrophages. The availability of palmitate however, was not associated with a reduction of glucose or glutamine consumption. The cycle of interconversion, free fatty acids/triacyglycerol in Kupffer cells from tumour-bearing rats was also found to be increased, as was hydrogen peroxide production. Taken together the results suggest an increased utilization of substrates for both energy production and for synthetic processes (e.g. NADPH for hydrogen peroxide production). © 1998 John Wiley & Sons, Ltd. 相似文献
995.
Ettore Benedetti Michele Saviano Rosa Iacovino Carlo Pedone Antonello Santini Marco Crisma Fernando Formaggio Claudio Toniolo Quirinus B. Broxterman Johan Kamphuis 《Biopolymers》1998,46(7):433-443
The crystal-state preferred conformations of six Nα-blocked pentapeptide esters, each containing four helicogenic, achiral α-aminoisobutyric acid (Aib) residues followed by one chiral L -valine (L -Val) or Cα-methyl-L -valine [(αMe)Val] residue at the C-terminus, have been assessed by x-ray diffraction analysis. In all of the compounds the (Aib)4 sequence is folded in a regular 310-helical conformation. In the four pentapeptides characterized by the L -(αMe)Val residue two conformationally distinct molecules occur in the asymmetric unit. Conversely, only one molecule is observed in the asymmetric unit of two pentapeptides with the C-terminal L -Val residue. In the L -Val based peptides the helical screw sense of the (Aib)4 sequence is right-handed, whereas in the L (αMe)Val analogues both right- and left-handed helical screw senses concomitantly occur in the two crystallographically independent molecules. © 1998 John Wiley & Sons, Inc. Biopoly 46: 433–443, 1998 相似文献
996.
Murray Goodman Ralph-Heiko Mattern Peter Gantzel Antonello Santini Rosa Iacovino Michele Saviano Ettore Benedetti 《Journal of peptide science》1998,4(4):229-238
The molecular basis of sweet taste was investigated by carrying out the crystal state conformational analysis by X-ray diffraction of the following dipeptide taste igands:N-3,3-dimethylbutyl-aspartyl-phenylalanine methyl ester, I (N-DMB-Asp-Phe-OMe), its sodium salt (N-DMB-Asp-Phe-ONa), II , aspartyl-D -2-aminobutyric acid-(S)-α-ethylbenzylamide, III (Asp-D -Abu-(S)-α-ethylbenzylamide), aspartyl-N′-((2,2,5,5-tetramethylcyclopentanyl)-carbonyl)-(R)-1,1-diamino-ethane, IV (Asp-(R)-gAla-TMCP), and aspartyl-D -valine-(R)-α-methoxymethylbenzyl amide, V (Asp-D -Val-(R)-α-methoxymethylbenzylamide). With the exception of the sodium salt II , all compounds are sweet-tasting, showing in some cases considerable potency enhancement with respect to sucrose. The results of this study confirm the earlier model that an ‘L-shape’ molecular array is essential for eliciting sweet taste for dipeptide-like ligands. In addition, it was established that (i) substitution of the N-terminal group does not inhibit sweet taste, if its zwitterionic character is maintained; (ii) a hydrophobic group located between the stem and the base of the L-shape could be responsible for sweetness potency enhancement, as found in I, III and IV ; in fact, the extraordinary potency of the N-alkylated analogue I would support a model with an additional hydrophobic binding domain above the base of the ‘L’; (iii) removal of the methyl ester at the C-terminus of compound I with the salt formation gives rise to the tasteless compound II ; (iv) for the first time all possible side-chain conformers (g−,g+andt) for the N-substituted aspartyl residue were observed; and (v) a retro-inverso modification, incorporated at position 2 of the dipeptide chain, confers greater flexibility to the molecule, as demonstrated by the contemporary presence of six conformationally distinct independent molecules in the unit cell and yet sweet taste properties are maintained, as found in IV . © 1998 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
997.
Adriana Marcelo Inês T. Afonso Ricardo Afonso-Reis David V. C. Brito Rafael G. Costa Ana Rosa Joo Alves-Cruzeiro Benedita Ferreira Carina Henriques Rui J. Nobre Carlos A. Matos Luís Pereira de Almeida Clvio Nbrega 《Cell death & disease》2021,12(12)
Spinocerebellar ataxia type 2 (SCA2) is an incurable and genetic neurodegenerative disorder. The disease is characterized by progressive degeneration of several brain regions, resulting in severe motor and non-motor clinical manifestations. The mutation causing SCA2 disease is an abnormal expansion of CAG trinucleotide repeats in the ATXN2 gene, leading to a toxic expanded polyglutamine segment in the translated ataxin-2 protein. While the genetic cause is well established, the exact mechanisms behind neuronal death induced by mutant ataxin-2 are not yet completely understood. Thus, the goal of this study is to investigate the role of autophagy in SCA2 pathogenesis and investigate its suitability as a target for therapeutic intervention. For that, we developed and characterized a new striatal lentiviral mouse model that resembled several neuropathological hallmarks observed in SCA2 disease, including formation of aggregates, neuronal marker loss, cell death and neuroinflammation. In this new model, we analyzed autophagic markers, which were also analyzed in a SCA2 cellular model and in human post-mortem brain samples. Our results showed altered levels of SQSTM1 and LC3B in cells and tissues expressing mutant ataxin-2. Moreover, an abnormal accumulation of these markers was detected in SCA2 patients’ striatum and cerebellum. Importantly, the molecular activation of autophagy, using the compound cordycepin, mitigated the phenotypic alterations observed in disease models. Overall, our study suggests an important role for autophagy in the context of SCA2 pathology, proposing that targeting this pathway could be a potential target to treat SCA2 patients.Subject terms: Diseases of the nervous system, Molecular neuroscience 相似文献
998.
Latitudinal and altitudinal patterns of plant community diversity on mountain summits across the tropical Andes 下载免费PDF全文
Francisco Cuesta Priscilla Muriel Luis Daniel Llambí Stephan Halloy Nikolay Aguirre Stephan Beck Julieta Carilla Rosa Isela Meneses Soledad Cuello Alfredo Grau Luis E. Gámez Javier Irazábal Jorge Jácome Ricardo Jaramillo Lirey Ramírez Natalia Samaniego David Suárez‐Duque Natali Thompson Alfredo Tupayachi Paul Viñas Karina Yager María T. Becerra Harald Pauli William D. Gosling 《Ecography》2017,40(12):1381-1394
The high tropical Andes host one of the richest alpine floras of the world, with exceptionally high levels of endemism and turnover rates. Yet, little is known about the patterns and processes that structure altitudinal and latitudinal variation in plant community diversity. Herein we present the first continental‐scale comparative study of plant community diversity on summits of the tropical Andes. Data were obtained from 792 permanent vegetation plots (1 m2) within 50 summits, distributed along a 4200 km transect; summit elevations ranged between 3220 and 5498 m a.s.l. We analyzed the plant community data to assess: 1) differences in species abundance patterns in summits across the region, 2) the role of geographic distance in explaining floristic similarity and 3) the importance of altitudinal and latitudinal environmental gradients in explaining plant community composition and richness. On the basis of species abundance patterns, our summit communities were separated into two major groups: Puna and Páramo. Floristic similarity declined with increasing geographic distance between study‐sites, the correlation being stronger in the more insular Páramo than in the Puna (corresponding to higher species turnover rates within the Páramo). Ordination analysis (CCA) showed that precipitation, maximum temperature and rock cover were the strongest predictors of community similarity across all summits. Generalized linear model (GLM) quasi‐Poisson regression indicated that across all summits species richness increased with maximum air temperature and above‐ground necromass and decreased on summits where scree was the dominant substrate. Our results point to different environmental variables as key factors for explaining vertical and latitudinal species turnover and species richness patterns on high Andean summits, offering a powerful tool to detect contrasting latitudinal and altitudinal effects of climate change across the tropical Andes. 相似文献
999.
Michele De Rosa Jannick Schmidt Miguel Brandão Massimo Pizzol 《The International Journal of Life Cycle Assessment》2017,22(2):172-184
Purpose
Despite a mature debate on the importance of a time-dependent account of carbon fluxes in life cycle assessments (LCA) of forestry products, static accounts of fluxes are still common. Time-explicit inventory of carbon fluxes is not available to LCA practitioners, since the most commonly used life cycle inventory (LCI) databases use a static approach. Existing forest models are typically applied to specific study fields for which the detailed input parameters required are available. This paper presents a simplified parametric model to obtain a time-explicit balanced account of the carbon fluxes in a forest for use in LCA. The model was applied to the case of spruce as an example.Methods
The model calculated endogenous and exogenous carbon fluxes in tons of carbon per hectare. It was designed to allow users to choose (a) the carbon pools to be included in the analysis (aboveground and belowground carbon pools, only aboveground carbon or only carbon in stem); (b) a linear or sigmoidal dynamic function describing biomass growth; (c) a sigmoidal, negative exponential or linear dynamic function describing independently the decomposition of aboveground and belowground biomass; and (d) the forest management features such as stand type, rotation time, thinning frequency and intensity.Results and discussion
The parametric model provides a time-dependent LCI of forest carbon fluxes per unit of product, taking into account the typically limited data available to LCA practitioners, while providing consistent and robust outcomes. The results obtained for the case study were validated with the more complex CO2FIX. The model ensures carbon balance within spatial and time delimitation defined by the user by accounting for the annual biomass degradation and production in each carbon pool. The inventory can be used in LCA studies and coupled with classic indicators (e.g. global warming potential) to accurately determine the climate impacts over time. The model is applicable globally and to any forest management practice.Conclusions
This paper proposes a simplified and flexible forest model, which facilitates the implementation in LCA of time-dependent assessments of bio-based products.1000.
Identification of a sex‐specific molecular marker in Salminus brasiliensis (Characiformes) based on SCAR marker 下载免费PDF全文
L. De Rosa V. P. Cruz E. A. Serrano N. J. Mendes A. P. Wasko J. A. Senhorini B. G. Pardo P. Martínez C. Oliveira F. Foresti 《Zeitschrift fur angewandte Ichthyologie》2017,33(5):1024-1026
Salminus brasiliensis, a characin regionally named ‘dourado’ (meaning goldfish), is the biggest characid fish, this species is cited in a list of fishes that are vulnerable. The goal of the present work was to try to identify, through AFLP technique to convert them into single locus markers (SCARs), in order to improve the sex identification in S. brasiliensis. Between possible sex‐specific AFLP markers in this study, one male‐specific were isolated (Les1) and converted into a SCAR marker. Les1 marker was confirmed sex‐specific in all samples tested. A sex‐specific DNA marker applicable to fish would be very useful for elucidating sex determination mechanism in fish. 相似文献