全文获取类型
收费全文 | 8365篇 |
免费 | 610篇 |
国内免费 | 3篇 |
专业分类
8978篇 |
出版年
2023年 | 48篇 |
2022年 | 97篇 |
2021年 | 185篇 |
2020年 | 116篇 |
2019年 | 133篇 |
2018年 | 184篇 |
2017年 | 199篇 |
2016年 | 281篇 |
2015年 | 439篇 |
2014年 | 459篇 |
2013年 | 535篇 |
2012年 | 658篇 |
2011年 | 561篇 |
2010年 | 371篇 |
2009年 | 339篇 |
2008年 | 430篇 |
2007年 | 476篇 |
2006年 | 429篇 |
2005年 | 383篇 |
2004年 | 370篇 |
2003年 | 344篇 |
2002年 | 326篇 |
2001年 | 119篇 |
2000年 | 80篇 |
1999年 | 119篇 |
1998年 | 97篇 |
1997年 | 68篇 |
1996年 | 61篇 |
1995年 | 67篇 |
1994年 | 64篇 |
1993年 | 65篇 |
1992年 | 68篇 |
1991年 | 70篇 |
1990年 | 69篇 |
1989年 | 46篇 |
1988年 | 44篇 |
1987年 | 21篇 |
1986年 | 35篇 |
1985年 | 35篇 |
1984年 | 38篇 |
1983年 | 25篇 |
1982年 | 36篇 |
1981年 | 29篇 |
1980年 | 20篇 |
1979年 | 24篇 |
1978年 | 20篇 |
1977年 | 23篇 |
1976年 | 22篇 |
1975年 | 19篇 |
1974年 | 22篇 |
排序方式: 共有8978条查询结果,搜索用时 15 毫秒
861.
Crystel Bonnet M’hamed Grati Sandrine Marlin Jacqueline Levilliers Jean-Pierre Hardelin Marine Parodi Magali Niasme-Grare Diana Zelenika Marc Délépine Delphine Feldmann Laurence Jonard Aziz El-Amraoui Dominique Weil Bruno Delobel Christophe Vincent Hélène Dollfus Marie-Madeleine Eliot Albert David Catherine Calais Jacqueline Vigneron Bettina Montaut-Verient Dominique Bonneau Jacques Dubin Christel Thauvin Alain Duvillard Christine Francannet Thierry Mom Didier Lacombe Françoise Duriez Valérie Drouin-Garraud Marie-Françoise Thuillier-Obstoy Sabine Sigaudy Anne-Marie Frances Patrick Collignon Georges Challe Rémy Couderc Mark Lathrop José-Alain Sahel Jean Weissenbach Christine Petit Françoise Denoyelle 《Orphanet journal of rare diseases》2011,6(1):1-19
Background
Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.Methods
We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).Results
Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.Conclusions
Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy. 相似文献862.
Yannis Cuypers Brigitte Vin?on-Leite Alexis Groleau Bruno Tassin Jean-Fran?ois Humbert 《The ISME journal》2011,5(4):580-589
The vertical and horizontal distribution of the cyanobacterium, Planktothrix rubescens, was studied in a deep alpine lake (Lac du Bourget) in a 2-year monitoring program with 11 sampling points, and a 24-h survey at one sampling station. This species is known to proliferate in the metalimnic layer of numerous deep mesotrophic lakes in temperate areas, and also to produce hepatotoxins. When looking at the distribution of P. rubescens at the scale of the entire lake, we found large variations (up to 10 m) in the depth of the biomass peak in the water column. These variations were closely correlated to isotherm displacements. We also found significant variations in the distribution of the cyanobacterial biomass in the northern and southern parts of the lake. We used a physical modeling approach to demonstrate that two internal wave modes can explain these variations. Internal waves are generated by wind events, but can still be detected several days after the end of these events. Finally, our 24-h survey at one sampling point demonstrated that the V1H1 sinusoidal motion could evolve into nonlinear fronts. All these findings show that internal waves have a major impact on the distribution of P. rubescens proliferating in the metalimnic layer of a deep lake, and that this process could influence the growth of this species by a direct impact on light availability. 相似文献
863.
Alvarez-Suarez JM Dekanski D Ristić S Radonjić NV Petronijević ND Giampieri F Astolfi P González-Paramás AM Santos-Buelga C Tulipani S Quiles JL Mezzetti B Battino M 《PloS one》2011,6(10):e25878
Background and Aim
Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa.Methods/Principal Findings
Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found.Conclusions
Strawberry extracts prevented exogenous ethanol-induced damage to rats'' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species. 相似文献864.
Background
Although leishmaniases are regarded as serious public health issues in the State of Tocantins, as consequence of the impact of environmental changes, small advances in taxonomic and ecological studies of Phlebotominae fauna are taking place in this state. The present study aimed to improve the knowledge about the sand flies, as well as about the aspects of the bioecology of leishmaniases vectors from Porto Nacional, a city that was directly impacted by the construction of Luís Eduardo Magalhães Hydroelectric Plant (HEP – Lajeado).Methodology/Principal Findings
Sand flies were collected monthly using CDC light traps and Shannon traps for a period of 40 consecutive months, at different monitoring stations, where 7162 specimens were collected and 48 species were detected. Among the species found, 22 are first records in the state and seven are considered important vectors of leishmaniases. Lutzomyia longipalpis, the vector of American Visceral Leishmaniasis (AVL) showed higher frequency in urban compared to rural areas, and Nyssomyia whitmani, the vector of American Cutaneous Leishmaniasis (ACL), predominated in rural areas. The frequency and habits of sand fly vectors are discussed considering environmental characteristics and climatic factors.Conclusions/Significance
The construction of dams requires a great amount of labor, therefore attracting people from elsewhere. Increased migration, without adequate structure, leads to bad living conditions in new and unplanned settlements. It also leads to deforestation associated with environmental impacts, which can facilitate the spread of leishmaniases.This study discusses the importance of Lu. longipalpis and Ny. whitmani on the transmission cycles of leishmaniases in Porto Nacional and the record of Bi. flaviscutellata in periurban area of the city. 相似文献865.
866.
Background
The haptic perception of ground compliance is used for stable regulation of dynamic posture and the control of locomotion in diverse natural environments. Although rarely investigated in relation to walking, vibrotactile sensory channels are known to be active in the discrimination of material properties of objects and surfaces through touch. This study investigated how the perception of ground surface compliance is altered by plantar vibration feedback.Methodology/Principal Findings
Subjects walked in shoes over a rigid floor plate that provided plantar vibration feedback, and responded indicating how compliant it felt, either in subjective magnitude or via pairwise comparisons. In one experiment, the compliance of the floor plate was also varied. Results showed that perceived compliance of the plate increased monotonically with vibration feedback intensity, and depended to a lesser extent on the temporal or frequency distribution of the feedback. When both plate stiffness (inverse compliance) and vibration amplitude were manipulated, the effect persisted, with both factors contributing to compliance perception. A significant influence of vibration was observed even for amplitudes close to psychophysical detection thresholds.Conclusions/Significance
These findings reveal that vibrotactile sensory channels are highly salient to the perception of surface compliance, and suggest that correlations between vibrotactile sensory information and motor activity may be of broader significance for the control of human locomotion than has been previously acknowledged. 相似文献867.
María B. Yossen Mariana Lozada Marcelo N. Kuperman Silvia Gonzlez Bruno Gastaldi Micaela Buteler 《Journal of Applied Entomology》2019,143(6):635-643
Recently, plant‐based repellents have been proposed as a potential alternative to classic pesticides against pest wasps, in certain scenarios. Here, the repellent effect of Dysphania multifida essential oil and one of its main terpenoid components, α‐terpinene, were tested under field conditions with natural populations of wasps in Patagonia Argentina. D. multifida essential oil (paico), as well as α‐terpinene, repelled V. germanica wasps in the field. A strong avoidance of food baits treated with the essential oil or α‐terpinene was observed in choice and no‐choice tests. In no‐choice tests, the time it took wasps to arrive at the bait was significantly greater in treated baits than in control baits. Also, the total number of arriving wasps in 30 min was significantly greater in untreated baits in comparison with treated baits, under similar environmental conditions and wasp density. As the wasps’ flight season progressed, wasp density and motivation for proteinaceous food sources increased. This was evidenced by a greater total number of wasps in untreated baits with time. On the contrary, the number of wasps in treated baits remained low throughout the peak season. Both the paico essential oil and the α‐terpinene act as powerful repellents for V. germanica wasps, generating an avoidance response to treated food sources. Thus, these compounds have potential to be used as repellents to prevent wasps’ approaches and foraging, when applied in close proximity to a food source. 相似文献
868.
Els Lommelen Tom Wenseleers Christine A. Johnson Falko P. Drijfhout Johan Billen Bruno Gobin 《Journal of Insect Behavior》2010,23(3):236-249
Approximately 150 ant species are facultatively or obligately queenless whereby mated workers assume the role of the queen.
In many of these species a reproductive dominance hierarchy is established by way of aggressive interactions. Top-ranking
workers, which are typically the most fecund, acquire a characteristic cuticular hydrocarbon profile. We studied the temporal
dynamics of this chemical change and associated interplay with observed aggressive interactions in an experimentally orphaned
colony of the facultatively queenless ant Gnamptogenys striatula. Our observations and chemical analyses demonstrate that chemical fertility signals played a major role in the establishment
of a dominance hierarchy and aggression settled dominance relationships only when ants had identical hydrocarbon profiles.
Moreover, individuals with a higher potential fertility, in this experiment reflected in a higher ovariole number, are shown
to have a better chance of becoming a reproductive. 相似文献
869.
Ras-GAP Controls Rho-Mediated Cytoskeletal Reorganization through Its SH3 Domain 总被引:5,自引:3,他引:5 下载免费PDF全文
Vronique Leblanc Bruno Tocque Isabelle Delumeau 《Molecular and cellular biology》1998,18(9):5567-5578
Proteins of the Ras superfamily, Ras, Rac, Rho, and Cdc42, control the remodelling of the cortical actin cytoskeleton following growth factor stimulation. A major regulator of Ras, Ras-GAP, contains several structural motifs, including an SH3 domain and two SH2 domains, and there is evidence that they harbor a signalling function. We have previously described a monoclonal antibody to the SH3 domain of Ras-GAP which blocks Ras signalling in Xenopus oocytes. We now show that microinjection of this antibody into Swiss 3T3 cells prevents the formation of actin stress fibers stimulated by growth factors or activated Ras, but not membrane ruffling. This inhibition is bypassed by coinjection of activated Rho, suggesting that the Ras-GAP SH3 domain is necessary for endogenous Rho activation. In agreement, the antibody blocks lysophosphatidic acid-induced neurite retraction in differentiated PC12 cells. Furthermore, we demonstrate that microinjection of full-length Ras-GAP triggers stress fiber polymerization in fibroblasts in an SH3-dependent manner, strongly suggesting an effector function besides its role as a Ras downregulator. These results support the idea that Ras-GAP connects the Ras and Rho pathways and, therefore, regulates the actin cytoskeleton through a mechanism which probably does not involve p190 Rho-GAP. 相似文献
870.
Pelaia G Gallelli L D'Agostino B Vatrella A Cuda G Fratto D Renda T Galderisi U Piegari E Crimi N Rossi F Caputi M Costanzo FS Vancheri C Maselli R Marsico SA 《Journal of cellular physiology》2007,210(2):489-497
Transforming growth factor-beta1 (TGF-beta1) is crucially involved in the fibrotic events characterizing interstitial lung diseases (ILDs), as well as in the airway remodeling process typical of asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal and fibrotic human lung fibroblasts (HLFs), the effects of TGF-beta1 on mitogen-activated protein kinase (MAPK) phosphorylation, cell proliferation, and production of interleukins 6 (IL-6) and 11 (IL-11), in the presence or absence of a pretreatment with budesonide (BUD). MAPK phosphorylation was detected by Western blotting, cell viability and proliferation were evaluated using Trypan blue staining and [(3)H]-thymidine incorporation assay, respectively, and the release of IL-6 and IL-11 into cell culture supernatants was assessed by ELISA. TGF-beta1 (10 ng/ml) significantly stimulated MAPK phosphorylation (P < 0.01), and also enhanced cell proliferation as well as the secretion of both IL-6 and IL-11, which reached the highest increases at the 72nd h of cell exposure to this growth factor. All such effects were prevented by BUD (10(-8) M) and, with the exception of IL-6 release, also by a mixture of MAPK inhibitors. Therefore, our findings suggest that the fibrotic action exerted by TGF-beta1 in the lung is mediated at least in part by MAPK activation and by an increased synthesis of the profibrogenic cytokines IL-6 and IL-11; all these effects appear to be prevented by corticosteroids via inhibition of MAPK phosphorylation. 相似文献