全文获取类型
收费全文 | 4121篇 |
免费 | 340篇 |
出版年
2023年 | 15篇 |
2022年 | 44篇 |
2021年 | 110篇 |
2020年 | 82篇 |
2019年 | 88篇 |
2018年 | 81篇 |
2017年 | 86篇 |
2016年 | 145篇 |
2015年 | 199篇 |
2014年 | 226篇 |
2013年 | 277篇 |
2012年 | 357篇 |
2011年 | 343篇 |
2010年 | 192篇 |
2009年 | 152篇 |
2008年 | 268篇 |
2007年 | 212篇 |
2006年 | 201篇 |
2005年 | 193篇 |
2004年 | 161篇 |
2003年 | 148篇 |
2002年 | 127篇 |
2001年 | 52篇 |
2000年 | 57篇 |
1999年 | 41篇 |
1998年 | 36篇 |
1997年 | 42篇 |
1996年 | 28篇 |
1995年 | 26篇 |
1994年 | 28篇 |
1993年 | 20篇 |
1992年 | 26篇 |
1991年 | 34篇 |
1990年 | 27篇 |
1989年 | 25篇 |
1988年 | 27篇 |
1987年 | 21篇 |
1986年 | 20篇 |
1985年 | 15篇 |
1984年 | 17篇 |
1983年 | 10篇 |
1982年 | 15篇 |
1981年 | 14篇 |
1979年 | 9篇 |
1978年 | 10篇 |
1976年 | 9篇 |
1975年 | 17篇 |
1973年 | 12篇 |
1972年 | 7篇 |
1968年 | 17篇 |
排序方式: 共有4461条查询结果,搜索用时 31 毫秒
81.
Differences in the chitinolytic activity of mammalian chitinases on soluble and insoluble substrates
Benjamin A. Barad Lin Liu Roberto E. Diaz Ralp Basilio Steven J. Van Dyken Richard M. Locksley James S. Fraser 《Protein science : a publication of the Protein Society》2020,29(4):952-963
Chitin is an abundant polysaccharide used by many organisms for structural rigidity and water repulsion. As such, the insoluble crystalline structure of chitin poses significant challenges for enzymatic degradation. Acidic mammalian chitinase, a processive glycosyl hydrolase, is the primary enzyme involved in the degradation of environmental chitin in mammalian lungs. Mutations to acidic mammalian chitinase have been associated with asthma, and genetic deletion in mice increases morbidity and mortality with age. We initially set out to reverse this phenotype by engineering hyperactive acidic mammalian chitinase variants. Using a screening approach with commercial fluorogenic substrates, we identified mutations with consistent increases in activity. To determine whether the activity increases observed were consistent with more biologically relevant chitin substrates, we developed new assays to quantify chitinase activity with insoluble chitin, and identified a one‐pot fluorogenic assay that is sufficiently sensitive to quantify changes to activity due to the addition or removal of a carbohydrate‐binding domain. We show that the activity increases from our directed evolution screen were lost when insoluble substrates were used. In contrast, naturally occurring gain‐of‐function mutations gave similar results with oligomeric and insoluble substrates. We also show that activity differences between acidic mammalian chitinase and chitotriosidase are reduced with insoluble substrate, suggesting that previously reported activity differences with oligomeric substrates may have been driven by differential substrate specificity. These results highlight the need for assays against physiological substrates when engineering metabolic enzymes, and provide a new one‐pot assay that may prove to be broadly applicable to engineering glycosyl hydrolases. 相似文献
82.
83.
Lucy E. Ridding Adrian C. Newton Sally A. Keith Robin M. Walls Anita Diaz Richard F. Pywell James M. Bullock 《Ecography》2021,44(1):33-43
The extinction debt, delayed species extinctions following landscape degradation, is a widely discussed concept. But a consensus about the prevalence of extinctions debts is hindered by a multiplicity of methods and a lack of comparisons among habitats. We applied three contrasting species–area relationship methods to test for plant community extinction debts in three habitats which had different degradation histories over the last century: calcareous grassland, heathland and woodland. These methods differ in their data requirements, with the first two using information on past and current habitat area alongside current species richness, whilst the last method also requires data on past species richness. The most data‐intensive, and hence arguably most reliable method, identified extinction debts across all habitats for specialist species, whilst the other methods did not. All methods detected an extinction debt in calcareous grassland, which had undergone the most severe degradation. We conclude that some methods failed to detect an extinction debt, particularly in habitats that have undergone moderate degradation. Data on past species numbers are required for the most reliable method; as such data are rare, extinction debts may be under‐reported. 相似文献
84.
Pedrotta Tiziana Gobet Erika Schwörer Christoph Beffa Giorgia Butz Christoph Henne Paul D. Morales-Molino César Pasta Salvatore van Leeuwen Jacqueline F. N. Vogel Hendrik Zwimpfer Elias Anselmetti Flavio S. Grosjean Martin Tinner Willy 《Vegetation History and Archaeobotany》2021,30(6):789-813
Vegetation History and Archaeobotany - Knowledge about the vegetation history of Sardinia, the second largest island of the Mediterranean, is scanty. Here, we present a new sedimentary record... 相似文献
85.
86.
Tóth Ákos Bata-Vidács Ildikó Kosztik Judit Máté Rózsa Kutasi József Tóth Erika Bóka Károly Táncsics András Nagy István Kovács Gábor Kukolya József 《Antonie van Leeuwenhoek》2021,114(10):1575-1584
Antonie van Leeuwenhoek - A Gram-reaction-negative halotolerant bacterial strain, designated Ka21T, was isolated from agricultural soil and characterised using a polyphasic approach to determine... 相似文献
87.
Kelly E. Leon Raquel Buj Elizabeth Lesko Erika S. Dahl Chi-Wei Chen Naveen Kumar Tangudu Yuka Imamura-Kawasawa Andrew V. Kossenkov Ryan P. Hobbs Katherine M. Aird 《The Journal of cell biology》2021,220(8)
Oncogene-induced senescence (OIS) is a stable cell cycle arrest that occurs in normal cells upon oncogene activation. Cells undergoing OIS express a wide variety of secreted factors that affect the senescent microenvironment termed the senescence-associated secretory phenotype (SASP), which is beneficial or detrimental in a context-dependent manner. OIS cells are also characterized by marked epigenetic changes. We globally assessed histone modifications of OIS cells and discovered an increase in the active histone marks H3K79me2/3. The H3K79 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) was necessary and sufficient for increased H3K79me2/3 occupancy at the IL1A gene locus, but not other SASP genes, and was downstream of STING. Modulating DOT1L expression did not affect the cell cycle arrest. Together, our studies establish DOT1L as an epigenetic regulator of the SASP, whose expression is uncoupled from the senescence-associated cell cycle arrest, providing a potential strategy to inhibit the negative side effects of senescence while maintaining the beneficial inhibition of proliferation. 相似文献
88.
Leonard Schmiester Yannik Schlte Frank T. Bergmann Tacio Camba Erika Dudkin Janine Egert Fabian Frhlich Lara Fuhrmann Adrian L. Hauber Svenja Kemmer Polina Lakrisenko Carolin Loos Simon Merkt Wolfgang Müller Dilan Pathirana Elba Raimúndez Lukas Refisch Marcus Rosenblatt Paul L. Stapor Philipp Stdter Dantong Wang Franz-Georg Wieland Julio R. Banga Jens Timmer Alejandro F. Villaverde Sven Sahle Clemens Kreutz Jan Hasenauer Daniel Weindl 《PLoS computational biology》2021,17(1)
Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been—so far—no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies. 相似文献
89.
C. Romero‐Diaz H. Richner F. Granado‐Lorencio B. Tschirren P. S. Fitze 《Journal of evolutionary biology》2013,26(3):635-646
Many colour ornaments are composite traits consisting of at least four components, which themselves may be more complex, determined by independent evolutionary pathways, and potentially being under different environmental control. To date, little evidence exists that several different components of colour elaboration are condition dependent and no direct evidence exists that different ornamental components are affected by different sources of variation. For example, in carotenoid‐based plumage colouration, one of the best‐known condition‐dependent ornaments, colour elaboration stems from both condition‐dependent pigment concentration and structural components. Some environmental flexibility of these components has been suggested, but specifically which and how they are affected remains unknown. Here, we tested whether multiple colour components may be condition dependent, by using a comprehensive 3 × 2 experimental design, in which we carotenoid supplemented and immune challenged great tit nestlings (Parus major) and quantified effects on different components of colouration. Plumage colouration was affected by an interaction between carotenoid availability and immune challenge. Path analyses showed that carotenoid supplementation increased plumage saturation via feather carotenoid concentration and via mechanisms unrelated to carotenoid deposition, while immune challenge affected feather length, but not carotenoid concentration. Thus, independent condition‐dependent pathways, affected by different sources of variation, determine colour elaboration. This provides opportunities for the evolution of multiple signals within components of ornamental traits. This finding indicates that the selective forces shaping the evolution of different components of a composite trait and the trait's signal content may be more complex than believed so far, and that holistic approaches are required for drawing comprehensive evolutionary conclusions. 相似文献
90.
Amilcar Chagas Freitas Júnior Paulo Henrique dos Santos Ching-Chang Ko Manoel Martín Júnior Erika Oliveira de Almeida 《Computer methods in biomechanics and biomedical engineering》2013,16(5):515-521
This study aimed to evaluate the influence of loading on a maxillary central incisor with the periodontal ligament (PDL) represented by 2D elastic beam elements using a 2D finite element analysis. Two models (M) were built varying the PDL representation: Mh (homogeneous PDL) and Mht (heterogeneous PDL with beam3 elements). Stress and displacements were determined for three loading conditions (L): Ll, lingual face loading at 45° with the tooth long axis; Li, perpendicular to the incisal edge; and Lip, on the incisal edge, parallel to the tooth long axis. Evaluation was performed on ANSYS software. Lip provided lower stress variation on the tooth and support structures when compared to Ll and Li. PDL's influence on stress values was lower for Lip. Oblique loading showed stress and displacement not observed in parallel loading condition through PDL's heterogeneous representation and it is probably incompatible with the in vivo condition. 相似文献