全文获取类型
收费全文 | 20134篇 |
免费 | 2004篇 |
国内免费 | 1583篇 |
出版年
2023年 | 454篇 |
2022年 | 396篇 |
2021年 | 490篇 |
2020年 | 673篇 |
2019年 | 840篇 |
2018年 | 838篇 |
2017年 | 743篇 |
2016年 | 722篇 |
2015年 | 715篇 |
2014年 | 1074篇 |
2013年 | 1383篇 |
2012年 | 881篇 |
2011年 | 990篇 |
2010年 | 763篇 |
2009年 | 920篇 |
2008年 | 943篇 |
2007年 | 1002篇 |
2006年 | 844篇 |
2005年 | 739篇 |
2004年 | 653篇 |
2003年 | 576篇 |
2002年 | 491篇 |
2001年 | 361篇 |
2000年 | 385篇 |
1999年 | 360篇 |
1998年 | 299篇 |
1997年 | 297篇 |
1996年 | 273篇 |
1995年 | 258篇 |
1994年 | 216篇 |
1993年 | 237篇 |
1992年 | 197篇 |
1991年 | 177篇 |
1990年 | 170篇 |
1989年 | 144篇 |
1988年 | 151篇 |
1987年 | 133篇 |
1986年 | 133篇 |
1985年 | 213篇 |
1984年 | 344篇 |
1983年 | 279篇 |
1982年 | 274篇 |
1981年 | 270篇 |
1980年 | 296篇 |
1979年 | 230篇 |
1978年 | 174篇 |
1977年 | 159篇 |
1976年 | 132篇 |
1975年 | 120篇 |
1974年 | 115篇 |
排序方式: 共有10000条查询结果,搜索用时 578 毫秒
931.
Mariano Alvarez Andrew Bleich Kathleen Donohue 《Evolution; international journal of organic evolution》2020,74(10):2265-2280
Phenotypes respond to environments experienced directly by an individual, via phenotypic plasticity, or to the environment experienced by ancestors, via transgenerational environmental effects. The adaptive value of environmental effects depends not only on the strength and direction of the induced response but also on how long the response persists within and across generations, and how stably it is expressed across environments that are encountered subsequently. Little is known about the genetic basis of those distinct components, or even whether they exhibit genetic variation. We tested for genetic differences in the inducibility, temporal persistence, and environmental stability of transgenerational environmental effects in Arabidopsis thaliana. Genetic variation existed in the inducibility of transgenerational effects on traits expressed across the life cycle. Surprisingly, the persistence of transgenerational effects into the third generation was uncorrelated with their induction in the second generation. Although environmental effects for some traits in some genotypes weakened over successive generations, others were stronger or even in the opposite direction in more distant generations. Therefore, transgenerational effects in more distant generations are not merely caused by the retention or dissipation of those expressed in prior generations, but they may be genetically independent traits with the potential to evolve independently. 相似文献
932.
Disturbance of wildlife is a potential cause of conservation concern, not least to overwintering waders Charadrii inhabiting estuaries close to conurbations where human recreational and economic activities are often concentrated. Disturbance from people on and alongside intertidal foraging areas could make it more difficult for birds to survive until spring in good condition by reducing the time available for foraging, increasing energy requirements and displacing birds to poorer foraging areas. We adopted a two-part approach to testing whether such significant impacts occurred in a Special Protection Area where disturbance risk was high because of its small size and close proximity to conurbations. In part one, we recorded over the whole estuary during stages of the tidal cycle when part or all of the intertidal zone was exposed and so accessible to waders (i.e. on receding, low and advancing tides): (1) the numbers and activities of people on the intertidal flats and on the adjacent land in those places where people were visible to waders in the intertidal zone and (2) the numbers of waders present and disturbed into flight, the flight distance and flight duration in the ‘overlap’ areas where people did disturb waders. People occurred on < 25% of the 938 ha of intertidal flats, but most waders foraged on mudflats, whereas most people were on sandflats. People on land were visible to foraging waders along < 35% of the 16.5 km of shoreline. Waders and people were therefore substantially separated in space. Within overlap areas, people and waders were often frequently separated in time: for example, people on land mostly disturbed waders when only the upper shore levels were exposed. The average overwintering wader spent < 0.1% of its foraging time during daylight flying away from people and the additional energy expenditure was equivalent to < 0.02% of its daily requirements. The comparison made in part two between our study area and two comparable estuaries showed that the number of visits each day to the overlap areas would need to be 29 or 43 times greater for disturbance to have lowered the birds’ body condition and winter survival. Both parts of the study therefore suggested strongly that the amount of disturbance was too trivial to have a significant impact on waders. It is concluded that: (1) to properly assess disturbance risk to waders, both extensive and intensive observations must be made on the behaviour of people and birds to quantify the extent to which they overlap in space and time, and (2) it should not be assumed that an estuary's close proximity to conurbations, and the presence of large numbers of people in the vicinity of the SPA, necessarily implies a significant disturbance risk to waders. 相似文献
933.
Lekha E. Manjunath Anumeha Singh Sarthak Sahoo Ashutosh Mishra Jinsha Padmarajan Chaithanya G. Basavaraju Sandeep M. Eswarappa 《The Journal of biological chemistry》2020,295(50):17009
Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3′ UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3′ UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential. 相似文献
934.
Nilüfer N. Turan Karni S. Moshal Karim Roder Brett C. Baggett Anatoli Y. Kabakov Saroj Dhakal Ryota Teramoto David Yi-Eng Chiang Mingwang Zhong An Xie Yichun Lu Samuel C. Dudley Jr. Calum A. MacRae Alain Karma Gideon Koren 《The Journal of biological chemistry》2020,295(52):18148
The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation. 相似文献
935.
Many behaviours have differential fitness consequences across thermal and ecological contexts, indicating that both ecological shifts and warming temperatures induced by climatic change may alter how organisms behave. However, empirical evidence of temperature-driven behavioural selection in natural systems is lacking. We compared behaviours and behavioural syndromes related to activity, exploration, boldness and aggression in populations of largemouth bass (Micropterus salmoides) from ambient lakes to the those from artificially warmed, power plant cooling lakes to investigate changes in behaviours associated with warmer environments. Activity, exploration, boldness and aggression of juvenile largemouth bass were assessed in laboratory conditions using a novel environment assay and a risky situation assay. We found that activity and exploratory behaviours were higher and decreased through first year ontogeny in populations from heated lakes, whereas these behaviours were lower and showed no relationship through ontogeny in populations from ambient lakes. We attribute these differences to the changes in food source availability in heated lakes associated with temperature-driven ecological effects. Bold and aggressive behaviours tended to differ between populations, as did correlations between behaviours, but did not differ between ambient and heated lakes. The findings of this work identify that large ecological changes associated with warming environments, such as food availability, may drive changes in some aspects of behavioural expression in largemouth bass but that other aspects of behavioural expression may be driven by lake-specific factors not related to warming. 相似文献
936.
This study describes a recreational fishing method focused on marine catfish, Genidens barbus (Endangered-EN), through the adoption of its eggs as a natural bait during its reproductive period in southern Brazilian ecosystems. Male G. barbus perform parental care, collecting eggs released by females after the fertilization process. Owing to this male behavioural pattern during the reproductive period, these individuals are easily caught in recreational fisheries that use eggs of the same species as a natural bait. The current adoption of G. barbus eggs as bait may intensify the fishing pressure on its populations. 相似文献
937.
Antônio B. Anderson Jean-Christophe Joyeux Sergio R. Floeter 《Journal of fish biology》2020,97(3):845-859
Biogeographical transition zones are important areas to investigate evolutionary ecological questions, but long-term population monitoring is needed to better understand ecological processes that govern population variations in such edge environments. The southernmost Brazilian rocky reefs are the southern limit of distribution for 96% of the tropical ichthyofauna of the western Atlantic. The Arvoredo Marine Biological Reserve is the only nearshore no-take marine-protected area (MPA) located in this transition zone. The main aim was to investigate how the populations of rocky reef fish species vary in density and biomass in space and over time, inside and outside the Arvoredo MPA. This study presents results based on a 9 year (2008–2017) underwater visual census monitoring study to evaluate the density and biomass of key fish species. Variations in density and biomass were detected for most species. Factors and mechanisms that may have influenced spatial variation are habitat structural complexity and protection from fisheries. Temporal variations, otherwise, may have been influenced by species proximity to their distributional limit, in synergy with density-dependent mechanisms and stochastic winter temperature oscillations. The MPAs harbour higher density and biomass for most species. Nonetheless, a prominent temporal decline in the recruitment of Epinephelus marginatus calls into question the continuous effectiveness of the MPA. 相似文献
938.
S100A9 is a calcium binding protein with multiple ligands and post-translation modifications that is involved in inflammatory events and the initial development of the cancer cell through to the development of metastatic disease. This review has a threefold purpose: 1) describe the S100A9 structural elements important for its biological activity, 2) describe the S100A9 biology in the context of the immune system, and 3) illustrate the role of S100A9 in the development of malignancy via interactions with the immune system and other cellular processes. 相似文献
939.
Hideaki Tagashira Chen Zhang Ying-mei Lu Hideyuki Hasegawa Hiroshi Kanai Feng Han Kohji Fukunaga 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
We previously reported that the σ1-receptor (σ1R) is down-regulated following cardiac hypertrophy and dysfunction in transverse aortic constriction (TAC) mice. Here we address how σ1R stimulation with the selective σ1R agonist SA4503 restores hypertrophy-induced cardiac dysfunction through σ1R localized in the sarcoplasmic reticulum (SR).Methods
We first confirmed anti-hypertrophic effects of SA4503 (0.1–1 μM) in cultured cardiomyocytes exposed to angiotensin II (Ang II). Then, to confirm the ameliorative effects of σ1R stimulation in vivo, we administered SA4503 (1.0 mg/kg) and the σ1R antagonist NE-100 (1.0 mg/kg) orally to TAC mice for 4 weeks (once daily).Results
σ1R stimulation with SA4503 significantly inhibited Ang II-induced cardiomyocyte hypertrophy. Ang II exposure for 72 h impaired phenylephrine (PE)-induced Ca2 + mobilization from the SR into both the cytosol and mitochondria. Treatment of cardiomyocytes with SA4503 largely restored PE-induced Ca2 + mobilization into mitochondria. Exposure of cardiomyocytes to Ang II for 72 h decreased basal ATP content and PE-induced ATP production concomitant with reduced mitochondrial size, while SA4503 treatment completely restored ATP production and mitochondrial size. Pretreatment with NE-100 or siRNA abolished these effects. Chronic SA4503 administration also significantly attenuated myocardial hypertrophy and restored ATP production in TAC mice. SA4503 administration also decreased hypertrophy-induced impairments in LV contractile function.Conclusions
σ1R stimulation with the specific agonist SA4503 ameliorates cardiac hypertrophy and dysfunction by restoring both mitochondrial Ca2 + mobilization and ATP production via σ1R stimulation.General significance
Our observations suggest that σ1R stimulation represents a new therapeutic strategy to rescue the heart from hypertrophic dysfunction. 相似文献940.
Yuanqing Hu Yuwei Shang Jinlin Huang Yan Wang Fangzhe Ren Yang Jiao Zhiming Pan Xin-an Jiao 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013