全文获取类型
收费全文 | 12583篇 |
免费 | 1019篇 |
国内免费 | 9篇 |
出版年
2023年 | 40篇 |
2022年 | 90篇 |
2021年 | 233篇 |
2020年 | 134篇 |
2019年 | 201篇 |
2018年 | 238篇 |
2017年 | 218篇 |
2016年 | 313篇 |
2015年 | 607篇 |
2014年 | 636篇 |
2013年 | 771篇 |
2012年 | 1052篇 |
2011年 | 1013篇 |
2010年 | 634篇 |
2009年 | 580篇 |
2008年 | 816篇 |
2007年 | 841篇 |
2006年 | 721篇 |
2005年 | 717篇 |
2004年 | 679篇 |
2003年 | 630篇 |
2002年 | 635篇 |
2001年 | 116篇 |
2000年 | 75篇 |
1999年 | 126篇 |
1998年 | 153篇 |
1997年 | 125篇 |
1996年 | 113篇 |
1995年 | 115篇 |
1994年 | 98篇 |
1993年 | 75篇 |
1992年 | 84篇 |
1991年 | 54篇 |
1990年 | 58篇 |
1989年 | 60篇 |
1988年 | 33篇 |
1987年 | 36篇 |
1986年 | 39篇 |
1985年 | 38篇 |
1984年 | 48篇 |
1983年 | 34篇 |
1982年 | 59篇 |
1981年 | 39篇 |
1980年 | 43篇 |
1979年 | 27篇 |
1978年 | 31篇 |
1977年 | 32篇 |
1976年 | 18篇 |
1975年 | 17篇 |
1973年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
231.
Joy H. Meserve Jessica C. Nelson Kurt C. Marsden Jerry Hsu Fabio A. Echeverry Roshan A. Jain Marc A. Wolman Alberto E. Pereda Michael Granato 《PLoS genetics》2021,17(6)
The acoustic startle response is an evolutionarily conserved avoidance behavior. Disruptions in startle behavior, particularly startle magnitude, are a hallmark of several human neurological disorders. While the neural circuitry underlying startle behavior has been studied extensively, the repertoire of genes and genetic pathways that regulate this locomotor behavior has not been explored using an unbiased genetic approach. To identify such genes, we took advantage of the stereotypic startle behavior in zebrafish larvae and performed a forward genetic screen coupled with whole genome analysis. We uncovered mutations in eight genes critical for startle behavior, including two genes encoding proteins associated with human neurological disorders, Dolichol kinase (Dolk), a broadly expressed regulator of the glycoprotein biosynthesis pathway, and the potassium Shaker-like channel subunit Kv1.1. We demonstrate that Kv1.1 and Dolk play critical roles in the spinal cord to regulate movement magnitude during the startle response and spontaneous swim movements. Moreover, we show that Kv1.1 protein is mislocalized in dolk mutants, suggesting they act in a common genetic pathway. Combined, our results identify a diverse set of eight genes, all associated with human disorders, that regulate zebrafish startle behavior and reveal a previously unappreciated role for Dolk and Kv1.1 in regulating movement magnitude via a common genetic pathway. 相似文献
232.
233.
Even with increasing interest in the ecological importance of intraspecific trait variation (ITV) for better understanding ecological processes, few studies have quantified ITV in seedlings and assessed constraints imposed by trade‐offs and correlations among individual‐level leaf traits. Estimating the amount and role of ITV in seedlings is important to understand tree recruitment and long‐term forest dynamics. We measured ten different size, economics, and whole leaf traits (lamina and petiole) for more than 2,800 seedlings (height ≥ 10 cm and diameter at breast height < 1 cm) in 283 seedling plots and then quantified the amount of ITV and trait correlations across two biological (intraspecific and interspecific) and spatial (within and among plots) scales. Finally, we explored the effects of trait variance and sample size on the strength of trait correlations. We found about 40% (6%–63%) variation in leaf‐level traits was explained by ITV across all traits. Lamina and petiole traits were correlated across biological and spatial scales, whereas leaf size traits (e.g., lamina area) were weakly correlated with economics traits (e.g., specific lamina area); lamina mass ratio was strongly related to the petiole length. Trait correlations varied among species, plots, and different scales but there was no evidence that the strength of trait relationships was stronger at broader than finer biological and spatial scales. While larger trait variance increased the strength of correlations, the sample size was the most important factor that was negatively related to the strength of trait correlations. Our results showed that a large amount of trait variation was explained by ITV, which highlighted the importance of considering ITV when using trait‐based approaches in seedling ecology. In addition, sample size was an important factor that influenced the strength of trait correlations, which suggests that comparing trait correlations across studies should consider the differences in sample size. 相似文献
234.
Xiangdong Xue Mayur K. Patel Chris Bailey Marc P.Y. Desmulliez 《Computer methods in biomechanics and biomedical engineering》2013,16(9):981-991
This article reports on the geometric optimisation of a T-shaped biochip microchannel fluidic separator aiming to maximise the separation efficiency of plasma from blood through the improvement of the unbalanced separation performance among different channel bifurcations. For this purpose, an algebraic analysis is firstly implemented to identify the key parameters affecting fluid separation. A numerical optimisation is then carried out to search the key parameters for improved separation performance of the biochip. Three parameters, the interval length between bifurcations, the main channel length from the outlet to the bifurcation region and the side channel geometry, are identified as the key characteristic sizes and defined as optimisation variables. A balanced flow rate ratio between the main and side channels, which is an indication of separation effectiveness, is defined as the objective. It is found that the degradation of the separation performance is caused by the unbalanced channel resistance ratio between the main and side channel routes from bifurcations to outlets. The effects of the three key parameters can be summarised as follows: (a) shortening the interval length between bifurcations moderately reduces the differences in the flow rate ratios; (b) extending the length of the main channel from the main outlet is effective for achieving a uniformity of flow rate ratio but ineffective in changing the velocity difference of the side channels and (c) decreasing the lengths of side channels from upstream to downstream is effective for both obtaining a uniform flow rate ratio and reducing the differences in the flow velocities between the side branch channels. An optimisation process combining the three parameters is suggested as this integration approach leads to fast convergent process and also offers flexible design options for satisfying different requirements. 相似文献
235.
Liana Tsiatsiani Evy Timmerman Pieter-Jan De Bock Dominique Vercammen Simon Stael Brigitte van de Cotte An Staes Marc Goethals Tine Beunens Petra Van Damme Kris Gevaert Frank Van Breusegem 《The Plant cell》2013,25(8):2831-2847
Metacaspases are distant relatives of the metazoan caspases, found in plants, fungi, and protists. However, in contrast with caspases, information about the physiological substrates of metacaspases is still scarce. By means of N-terminal combined fractional diagonal chromatography, the physiological substrates of METACASPASE9 (MC9; AT5G04200) were identified in young seedlings of Arabidopsis thaliana on the proteome-wide level, providing additional insight into MC9 cleavage specificity and revealing a previously unknown preference for acidic residues at the substrate prime site position P1′. The functionalities of the identified MC9 substrates hinted at metacaspase functions other than those related to cell death. These results allowed us to resolve the substrate specificity of MC9 in more detail and indicated that the activity of phosphoenolpyruvate carboxykinase 1 (AT4G37870), a key enzyme in gluconeogenesis, is enhanced upon MC9-dependent proteolysis. 相似文献
236.
Alexis Samba Mialoundama Nurul Jadid Julien Brunel Thomas Di Pascoli Dimitri Heintz Mathieu Erhardt Jér?me Mutterer Marc Bergdoll Daniel Ayoub Alain Van Dorsselaer Alain Rahier Paul Nkeng Philippe Geoffroy Michel Miesch Bilal Camara Florence Bouvier 《The Plant cell》2013,25(12):4879-4893
Sterols are vital for cellular functions and eukaryotic development because of their essential role as membrane constituents. Sterol biosynthetic intermediates (SBIs) represent a potential reservoir of signaling molecules in mammals and fungi, but little is known about their functions in plants. SBIs are derived from the sterol C4-demethylation enzyme complex that is tethered to the membrane by Ergosterol biosynthetic protein28 (ERG28). Here, using nonlethal loss-of-function strategies focused on Arabidopsis thaliana ERG28, we found that the previously undetected SBI 4-carboxy-4-methyl-24-methylenecycloartanol (CMMC) inhibits polar auxin transport (PAT), a key mechanism by which the phytohormone auxin regulates several aspects of plant growth, including development and responses to environmental factors. The induced accumulation of CMMC in Arabidopsis erg28 plants was associated with diagnostic hallmarks of altered PAT, including the differentiation of pin-like inflorescence, loss of apical dominance, leaf fusion, and reduced root growth. PAT inhibition by CMMC occurs in a brassinosteroid-independent manner. The data presented show that ERG28 is required for PAT in plants. Furthermore, it is accumulation of an atypical SBI that may act to negatively regulate PAT in plants. Hence, the sterol pathway offers further prospects for mining new target molecules that could regulate plant development. 相似文献
237.
Marc Verlaque 《Plant biosystems》2013,147(1-2):29-39
Abstract Studies on the genus Peyssonnelia (Rhodophyceae). X. Presence of Peyssonnelia codana (Rosenvinge) Denizot in the Mediterranean.—Peyssonnelia codana (Rosenvinge) Denizot, previously known only from Denmark, is recorded from the vicinity of a thermal power plant outlet (Martigues-Ponteau, Gulf of Fos, France). Mediterranean specimens are described and new details about the morphology of sporangial and sexual nemathecia are given. 相似文献
238.
239.
Fabrice Pagniez Hiam Abdala-Valencia Pascal Marchand Marc Le Borgne Guillaume Le Baut Sylvie Robert-Piessard 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):277-283
Two 3-(α-azolylbenzyl)indoles were evaluated against Leishmania amastigotes. Both compounds proved to be very active against intracellular and axenic amastigotes. The IC50 values of the imidazole derivative, PM17, and the triazole analogue, PM19, against L. mexicana axenic amastigotes, were 4.4 ± 0.1 and 6.4 ± 0.1 μM, respectively. Against intracellular amastigotes, PM17 produced a 66% decrease of leishmanial burden at 1 μM and PM19 had an IC50 of 1.3 μM. In a Balb/c mice model of L. major leishmaniasis, administration of PM17 led to a clear-cut parasite burden reduction: 98.9% in the spleen, 79.0% in the liver and 49.9% in the popliteal node draining the cutaneous lesion. As anticipated, it was brought to the fore that PM17 decreases ergosterol biosynthesis leading to membrane fungal cell alterations. Moreover it was proved that this imidazole antifungal agent induces a parasite burden-correlated decrease in interleukine-4 production both in the splenocyte and the popliteal node of the mouse. 相似文献
240.
Claudiu T. Supuran Andrea Scozzafava Marc A. Ilies Fabrizio Briganti 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):381-401
A new approach is proposed for the selective in vivo inhibition of membrane-bound versus cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes with a class of positively-charged, membrane-impermeant sulfonamides. Aromatic/heterocyclic sulfonamides acting as strong (but unselective) inhibitors of this zinc enzyme were derivatized by the attachment of trisub-stituted-pyridinium-ethylcarboxy moieties (obtained from 2, 4, 6–trisubstituted-pyrylium salts and β-alanine) to the amino, imino, hydrazino or hydroxyl groups present in their molecules. Efficient in vitro inhibition (in the nanomolar range) was observed with some of the new derivatives against three investigated CA isozymes, i.e., hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound isozyme; h = human; b = bovine isozyme). Due to their salt-like character, the new type of inhibitors reported here, unlike the classical, clinically used compounds (such as acetazolamide, methazolamide, ethoxzolamide), are unable to penetrate biological membranes, as shown by CJ vivo and in vivo perfusion experiments in rats. The level of bicarbonate excreted into the urine of the experimental animals perfused with solutions of the new and classical inhibitors suggest that: (i) when using the new type of positively-charged sulfonamides. only the membrane-bound enzyme (CA IV) was inhibited. whereas the cytosolic isozymes (CA I and II) were not affected, (ii) in the experiments in which the classical compounds (acetazolamide, bcn-zolamíde. etc.) were used. unselective inhibition of all CA isozymes (I. II and IV) occurred. 相似文献