全文获取类型
收费全文 | 6148篇 |
免费 | 441篇 |
国内免费 | 6篇 |
专业分类
6595篇 |
出版年
2023年 | 44篇 |
2022年 | 110篇 |
2021年 | 181篇 |
2020年 | 103篇 |
2019年 | 116篇 |
2018年 | 183篇 |
2017年 | 134篇 |
2016年 | 222篇 |
2015年 | 307篇 |
2014年 | 322篇 |
2013年 | 437篇 |
2012年 | 520篇 |
2011年 | 526篇 |
2010年 | 311篇 |
2009年 | 287篇 |
2008年 | 368篇 |
2007年 | 411篇 |
2006年 | 348篇 |
2005年 | 326篇 |
2004年 | 269篇 |
2003年 | 258篇 |
2002年 | 238篇 |
2001年 | 48篇 |
2000年 | 28篇 |
1999年 | 39篇 |
1998年 | 47篇 |
1997年 | 55篇 |
1996年 | 28篇 |
1995年 | 36篇 |
1994年 | 31篇 |
1993年 | 34篇 |
1992年 | 21篇 |
1991年 | 14篇 |
1990年 | 12篇 |
1989年 | 10篇 |
1988年 | 16篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 21篇 |
1983年 | 13篇 |
1982年 | 10篇 |
1981年 | 13篇 |
1980年 | 13篇 |
1978年 | 5篇 |
1977年 | 8篇 |
1976年 | 5篇 |
1975年 | 8篇 |
1973年 | 4篇 |
1960年 | 4篇 |
排序方式: 共有6595条查询结果,搜索用时 0 毫秒
91.
Benjamin H. Conlon Chedly Kastally Marina Kardell John Kefuss Robin F. A. Moritz Jarkko Routtu 《Ecology and evolution》2020,10(14):7806-7811
Parasitism is expected to select for counter‐adaptations in the host: driving a coevolutionary arms race. However, human interference between honey bees (Apis mellifera) and Varroa mites removes the effect of natural selection and restricts the evolution of host counter‐adaptations. With full‐sibling mating common among Varroa, this can rapidly select for virulent, highly inbred, Varroa populations. We investigated how the evolution of host resistance could affect the infesting population of Varroa mites. We screened a Varroa‐resistant honey bee population near Toulouse, France, for a Varroa resistance trait: the inhibition of Varroa's reproduction in drone pupae. We then genotyped Varroa which had co‐infested a cell using microsatellites. Across all resistant honey bee colonies, Varroa's reproductive success was significantly higher in co‐infested cells but the distribution of Varroa between singly and multiply infested cells was not different from random. While there was a trend for increased reproductive success when Varroa of differing haplotypes co‐infested a cell, this was not significant. This suggests local mate competition, through the presence of another Varroa foundress in a pupal cell, may be enough to help Varroa overcome host resistance traits; with a critical mass of infesting Varroa overwhelming host resistance. However, the fitness trade‐offs associated with preferentially co‐infesting cells may be too high for Varroa to evolve a mechanism to identify already‐infested cells. The increased reproductive success of Varroa when co‐infesting resistant pupal cells may act as a release valve on the selective pressure for the evolution of counter resistance traits: helping to maintain a stable host–parasite relationship. 相似文献
92.
Andriambeloson Jean-Basile Blanco Marina B. Andriantsalohimisantatra Ando Rivoharison Tahiry V. Walker Nathan Birkinshaw Chris Yoder Anne D. 《Primates; journal of primatology》2021,62(6):887-896
Primates - Habitat fragmentation is one of the major types of anthropogenic change, though fragmented landscapes predate human intervention. At present, the Central Highlands of Madagascar are... 相似文献
93.
Integrated requirement of non‐specific and sequence‐specific DNA binding in Myc‐driven transcription
94.
Eric R Beyerle Mohammadhasan Dinpajooh Huiying Ji Peter H von
Hippel Andrew H Marcus Marina G Guenza 《Nucleic acids research》2021,49(4):1872
Regulatory protein access to the DNA duplex ‘interior’ depends on local DNA ‘breathing’ fluctuations, and the most fundamental of these are thermally-driven base stacking-unstacking interactions. The smallest DNA unit that can undergo such transitions is the dinucleotide, whose structural and dynamic properties are dominated by stacking, while the ion condensation, cooperative stacking and inter-base hydrogen-bonding present in duplex DNA are not involved. We use dApdA to study stacking-unstacking at the dinucleotide level because the fluctuations observed are likely to resemble those of larger DNA molecules, but in the absence of constraints introduced by cooperativity are likely to be more pronounced, and thus more accessible to measurement. We study these fluctuations with a combination of Molecular Dynamics simulations on the microsecond timescale and Markov State Model analyses, and validate our results by calculations of circular dichroism (CD) spectra, with results that agree well with the experimental spectra. Our analyses show that the CD spectrum of dApdA is defined by two distinct chiral conformations that correspond, respectively, to a Watson–Crick form and a hybrid form with one base in a Hoogsteen configuration. We find also that ionic structure and water orientation around dApdA play important roles in controlling its breathing fluctuations. 相似文献
95.
Nir Hecht Caroline L Monteil Guy Perrire Marina Vishkautzan Eyal Gur 《Molecular biology and evolution》2021,38(3):761
The understanding of how proteins evolve to perform novel functions has long been sought by biologists. In this regard, two homologous bacterial enzymes, PafA and Dop, pose an insightful case study, as both rely on similar mechanistic properties, yet catalyze different reactions. PafA conjugates a small protein tag to target proteins, whereas Dop removes the tag by hydrolysis. Given that both enzymes present a similar fold and high sequence similarity, we sought to identify the differences in the amino acid sequence and folding responsible for each distinct activity. We tackled this question using analysis of sequence–function relationships, and identified a set of uniquely conserved residues in each enzyme. Reciprocal mutagenesis of the hydrolase, Dop, completely abolished the native activity, at the same time yielding a catalytically active ligase. Based on the available Dop and PafA crystal structures, this change of activity required a conformational change of a critical loop at the vicinity of the active site. We identified the conserved positions essential for stabilization of the alternative loop conformation, and tracked alternative mutational pathways that lead to a change in activity. Remarkably, all these pathways were combined in the evolution of PafA and Dop, despite their redundant effect on activity. Overall, we identified the residues and structural elements in PafA and Dop responsible for their activity differences. This analysis delineated, in molecular terms, the changes required for the emergence of a new catalytic function from a preexisting one. 相似文献
96.
Luana Lionetto Martina Ulivieri Matilde Capi Donatella De Bernardini Francesco Fazio Andrea Petrucca Leda Marina Pomes Ottavia De Luca Giovanna Gentile Barbara Casolla Martina Curto Gerardo Salerno Serena Schillizzi Maria Simona Torre Iolanda Santino Monica Rocco Paolo Marchetti Antonio Aceti Marina Borro 《生物化学与生物物理学报:疾病的分子基础》2021,1867(3):166042
Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention. 相似文献
97.
Nicola Chiarelli Nicoletta Zoppi Marco Ritelli Marina Venturini Daniele Capitanio Cecilia Gelfi Marina Colombi 《生物化学与生物物理学报:疾病的分子基础》2021,1867(4):166051
Hypermobile Ehlers-Danlos syndrome (hEDS), mainly characterized by generalized joint hypermobility and its complications, minor skin changes, and apparently segregating with an autosomal dominant pattern, is still without a known molecular basis. Hence, its diagnosis is only clinical based on a strict set of criteria defined in the revised EDS nosology. Moreover, the hEDS phenotypic spectrum is wide-ranging and comprises multiple associated signs and symptoms shared with other heritable or acquired connective tissue disorders and chronic inflammatory diseases. In this complex scenario, we previously demonstrated that hEDS patients' skin fibroblasts show phenotypic features of myofibroblasts, widespread extracellular matrix (ECM) disarray, perturbation of ECM-cell contacts, and dysregulated expression of genes involved in connective tissue architecture and related to inflammatory and pain responses. Herein, the cellular proteome of 6 hEDS dermal myofibroblasts was compared to that of 12 control fibroblasts to deepen the knowledge on mechanisms involved in the disease pathogenesis. Qualitative and quantitative differences were assessed based on top-down and bottom-up approaches and some differentially expressed proteins were proofed by biochemical analyses. Proteomics disclosed the differential expression of proteins principally implicated in cytoskeleton organization, energy metabolism and redox balance, proteostasis, and intracellular trafficking. Our findings offer a comprehensive view of dysregulated protein networks and related pathways likely associated with the hEDS pathophysiology. The present results can be regarded as a starting point for future in-depth investigations aimed to decipher the functional impact of potential bioactive molecules for the development of targeted management and therapies. 相似文献
98.
Loos Jacqueline Krauss Jochen Lyons Ashley Föst Stephanie Ohlendorf Constanze Racky Severin Röder Marina Hudel Lennart Herfert Volker Tscharntke Teja 《Biodiversity and Conservation》2021,30(8-9):2415-2432
Biodiversity and Conservation - Across Europe, calcareous grasslands become increasingly fragmented and their quality deteriorates through abandonment and land use intensification, both affecting... 相似文献
99.
100.
Sánchez-Hidalgo Marina León-González Antonio J. Gálvez-Peralta Marina González-Mauraza Nuria H. Martin-Cordero Carmen 《Phytochemistry Reviews》2021,20(1):225-226
Phytochemistry Reviews - In the original publication. 相似文献