全文获取类型
收费全文 | 2612篇 |
免费 | 177篇 |
专业分类
2789篇 |
出版年
2024年 | 3篇 |
2023年 | 21篇 |
2022年 | 42篇 |
2021年 | 87篇 |
2020年 | 50篇 |
2019年 | 57篇 |
2018年 | 79篇 |
2017年 | 54篇 |
2016年 | 107篇 |
2015年 | 166篇 |
2014年 | 212篇 |
2013年 | 223篇 |
2012年 | 255篇 |
2011年 | 255篇 |
2010年 | 158篇 |
2009年 | 127篇 |
2008年 | 170篇 |
2007年 | 149篇 |
2006年 | 117篇 |
2005年 | 109篇 |
2004年 | 90篇 |
2003年 | 80篇 |
2002年 | 69篇 |
2001年 | 15篇 |
2000年 | 11篇 |
1999年 | 16篇 |
1998年 | 13篇 |
1997年 | 7篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 8篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有2789条查询结果,搜索用时 15 毫秒
71.
Nucci NV Marques BS Bédard S Dogan J Gledhill JM Moorman VR Peterson RW Valentine KG Wand AL Wand AJ 《Journal of biomolecular NMR》2011,50(4):421-430
Comprehensive application of solution NMR spectroscopy to studies of macromolecules remains fundamentally limited by the molecular
rotational correlation time. For proteins, molecules larger than 30 kDa require complex experimental methods, such as TROSY
in conjunction with isotopic labeling schemes that are often expensive and generally reduce the potential information available.
We have developed the reverse micelle encapsulation strategy as an alternative approach. Encapsulation of proteins within
the protective nano-scale water pool of a reverse micelle dissolved in ultra-low viscosity nonpolar solvents overcomes the
slow tumbling problem presented by large proteins. Here, we characterize the contributions from the various components of
the protein-containing reverse micelle system to the rotational correlation time of the encapsulated protein. Importantly,
we demonstrate that the protein encapsulated in the reverse micelle maintains a hydration shell comparable in size to that
seen in bulk solution. Using moderate pressures, encapsulation in ultra-low viscosity propane or ethane can be used to magnify
this advantage. We show that encapsulation in liquid ethane can be used to reduce the tumbling time of the 43 kDa maltose
binding protein from ~23 to ~10 ns. These conditions enable, for example, acquisition of TOCSY-type data resolved on the adjacent
amide NH for the 43 kDa encapsulated maltose binding protein dissolved in liquid ethane, which is typically impossible for
proteins of such size without use of extensive deuteration or the TROSY effect. 相似文献
72.
COPI‐coated vesicles mediate retrograde membrane traffic from the cis‐Golgi to the endoplasmic reticulum (ER) in all eukaryotic cells. However, it is still unknown whether COPI vesicles fuse everywhere or at specific sites with the ER membrane. Taking advantage of the circumstance that the vesicles still carry their coat when they arrive at the ER, we have visualized active ER arrival sites (ERAS) by monitoring contact between COPI coat components and the ER‐resident Dsl tethering complex using bimolecular fluorescence complementation (BiFC). ERAS form punctate structures near Golgi compartments, clearly distinct from ER exit sites. Furthermore, ERAS are highly polarized in an actin and myosin V‐dependent manner and are localized near hotspots of plasma membrane expansion. Genetic experiments suggest that the COPI?Dsl BiFC complexes recapitulate the physiological interaction between COPI and the Dsl complex and that COPI vesicles are mistargeted in dsl1 mutants. We conclude that the Dsl complex functions in confining COPI vesicle fusion sites. 相似文献
73.
The cystathionine‐β‐synthase domains on the guanosine 5′’‐monophosphate reductase and inosine 5′‐monophosphate dehydrogenase enzymes from Leishmania regulate enzymatic activity in response to guanylate and adenylate nucleotide levels 下载免费PDF全文
Sabrina Smith Jan Boitz Ehzilan Subramanian Chidambaram Abhishek Chatterjee Maria Ait‐Tihyaty Buddy Ullman Armando Jardim 《Molecular microbiology》2016,100(5):824-840
The Leishmania guanosine 5′‐monophosphate reductase (GMPR) and inosine 5′‐monophosphate dehydrogenase (IMPDH) are purine metabolic enzymes that function maintaining the cellular adenylate and guanylate nucleotide. Interestingly, both enzymes contain a cystathionine‐β‐synthase domain (CBS). To investigate this metabolic regulation, the Leishmania GMPR was cloned and shown to be sufficient to complement the guaC (GMPR), but not the guaB (IMPDH), mutation in Escherichia coli. Kinetic studies confirmed that the Leishmania GMPR catalyzed a strict NADPH‐dependent reductive deamination of GMP to produce IMP. Addition of GTP or high levels of GMP induced a marked increase in activity without altering the Km values for the substrates. In contrast, the binding of ATP decreased the GMPR activity and increased the GMP Km value 10‐fold. These kinetic changes were correlated with changes in the GMPR quaternary structure, induced by the binding of GMP, GTP, or ATP to the GMPR CBS domain. The capacity of these CBS domains to mediate the catalytic activity of the IMPDH and GMPR provides a regulatory mechanism for balancing the intracellular adenylate and guanylate pools. 相似文献
74.
Céline Guien Gaëlle Blandin Pauline Lahaut Benoît Sanson Katia Nehal Sitraka Rabarimeriarijaona Rafaëlle Bernard Nicolas Lévy Sabrina Sacconi Christophe Béroud 《Orphanet journal of rare diseases》2018,13(1):218
Background
Facioscapulohumeral muscular dystrophy is a rare inherited neuromuscular disease with an estimated prevalence of 1/20,000 and France therefore harbors about 3000 FSHD patients. With research progress and the development of targeted therapies, patients’ identification through registries can facilitate and improve recruitment in clinical trials and studies.Results
The French National Registry of FSHD patients was designed as a mixed model registry involving both patients and physicians, through self-report and clinical evaluation questionnaires respectively, to collect molecular and clinical data. Because of the limited number of patients, data quality is a major goal of the registry and various automatic data control features have been implemented in the bioinformatics system. In parallel, data are manually validated by molecular and clinical curators. Since its creation in 2013, data from 638 FSHD patients have been collected, representing about 21% of the French FSHD population. The mixed model strategy allowed to collect 59.1% of data from both patients and clinicians; 26 and 14.9% from respectively patients and clinicians only. With the identification of the FSHD1 and FSHD2 forms, specific questionnaires have been designed. Though FSHD2 patients are progressively included, FSHD1 patients still account for the majority (94.9%). The registry is compatible with the FAIR principles as data are Findable, Accessible and Interoperable. We thus used molecular standards and standardized clinical terms used by the FILNEMUS French network of reference centers for the diagnosis and follow-up of patients suffering from a rare neuromuscular disease. The implemented clinical terms mostly map to dictionaries and terminology systems such as SNOMED-CT (75% of terms), CTV3 (61.7%) and NCIt (53.3%). Because of the sensitive nature of data, they are not directly reusable and can only be accessed as aggregated data after evaluation and approval by the registry oversight committee.Conclusions
The French National Registry of FSHD patients belongs to a national effort to develop databases, which should now interact with other initiatives to build a European and/or an international FSHD virtual registry for the benefits of patients. It is accessible at www.fshd.fr and various useful information, links, and documents, including a video, are available for patients and professionals.75.
Paulo Eduardo Menezes‐Silva Lucas Loram‐Loureno Rauander Douglas Ferreira Barros Alves Letícia Ferreira Sousa Sabrina Emanuella da Silva Almeida Fernanda Santos Farnese 《Ecology and evolution》2019,9(20):11979-11999
Anthropogenic activities such as uncontrolled deforestation and increasing greenhouse gas emissions are responsible for triggering a series of environmental imbalances that affect the Earth's complex climate dynamics. As a consequence of these changes, several climate models forecast an intensification of extreme weather events over the upcoming decades, including heat waves and increasingly severe drought and flood episodes. The occurrence of such extreme weather will prompt profound changes in several plant communities, resulting in massive forest dieback events that can trigger a massive loss of biodiversity in several biomes worldwide. Despite the gravity of the situation, our knowledge regarding how extreme weather events can undermine the performance, survival, and distribution of forest species remains very fragmented. Therefore, the present review aimed to provide a broad and integrated perspective of the main biochemical, physiological, and morpho‐anatomical disorders that may compromise the performance and survival of forest species exposed to climate change factors, particularly drought, flooding, and global warming. In addition, we also discuss the controversial effects of high CO2 concentrations in enhancing plant growth and reducing the deleterious effects of some extreme climatic events. We conclude with a discussion about the possible effects that the factors associated with the climate change might have on species distribution and forest composition. 相似文献
76.
Lisa N. Barrow Sabrina M. McNew Nora Mitchell Spencer C. Galen Holly L. Lutz Heather Skeen Thomas Valqui Jason D. Weckstein Christopher C. Witt 《Ecology letters》2019,22(6):987-998
Variation in susceptibility is ubiquitous in multi‐host, multi‐parasite assemblages, and can have profound implications for ecology and evolution in these systems. The extent to which susceptibility to parasites is phylogenetically conserved among hosts can be revealed by analysing diverse regional communities. We screened for haemosporidian parasites in 3983 birds representing 40 families and 523 species, spanning ~ 4500 m elevation in the tropical Andes. To quantify the influence of host phylogeny on infection status, we applied Bayesian phylogenetic multilevel models that included a suite of environmental, spatial, temporal, life history and ecological predictors. We found evidence of deeply conserved susceptibility across the avian tree; host phylogeny explained substantial variation in infection status, and results were robust to phylogenetic uncertainty. Our study suggests that susceptibility is governed, in part, by conserved, latent aspects of anti‐parasite defence. This demonstrates the importance of deep phylogeny for understanding present‐day ecological interactions. 相似文献
77.
Diogo Aparecido Lopes Silva Francisco Antonio Rocco Lahr Ana Laura Raymundo Pavan Yovana M. B. Saavedra Natalia Crespo Mendes Sabrina Rodrigues Sousa Roberta Sanches Aldo Roberto Ometto 《The International Journal of Life Cycle Assessment》2014,19(10):1767-1778
Purpose
Sugarcane bagasse is one of the main agro-industrial residues which can be used to produce wood-based panels. However, more investigations related to its environmental performance assessment are needed, focusing on questions such as: Does it provide environmental benefits? What are its main environmental impacts? Could it substitute wood as raw material? Accordingly, this paper presents a life cycle assessment (LCA) study of particle board manufactured with sugarcane bagasse residues.Methods
The cradle-to-gate assessment of 1 m3 of particle board made with sugarcane bagasse (PSB) considered three main subsystems: bagasse generation, bagasse distribution, and PSB production. For the inventory of PSB, dataset from two previous LCA studies related to the conventional particle board production and the ethanol life cycle for the Brazilian context were used. The allocation criterion for the bagasse generation subsystem was 9.08 % (economic base). The potential environmental impact phase was assessed by applying the CML and USEtox methods. PSB was compared with the conventional particle board manufactured in Brazil by the categories of the CML and USETox, and including land use indicators. Finally, two scenarios were analyzed to evaluate the influence of the allocation criteria and the consumption of sugarcane bagasse.Results and discussion
All hotspots identified by CML and USETox methods are mainly related to the PSB production subsystem (24–100 % of impacts) due to heavy fuel oil, electricity, and urea-formaldehyde resin supply chain. The bagasse generation subsystem was more relevant to the eutrophication category (75 % of impacts). The bagasse distribution subsystem was not relevant because the impacts on all categories were lower than 1 %. PSB can substitute the conventional particle board mainly because of its lower contribution to abiotic depletion and ecotoxicity. Regarding land use impacts, PSB showed lower values according to all indicators (38–40 % of all impacts), which is explained by the lower demand for land occupation in comparison to that of the traditional particle board.Conclusions
PSB can replace the traditional particle board due to its better environmental performance. The analysis of the economic allocation criterion was relevant only for the EP category, being important to reduce diesel and N-based fertilizers use during sugarcane cultivation. Regarding the influence of the sugarcane bagasse consumption, it is suggested that the sugarcane bagasse be mixed up to 75 % during particle board manufacturing so that good quality properties and environmental performance of panels can be provided. 相似文献78.
Sabrina C. Lachmann Tabea Mettler‐Altmann Alexander Wacker Elly Spijkerman 《Ecology and evolution》2019,9(3):1070-1082
In freshwaters, algal species are exposed to different inorganic nitrogen (Ni) sources whose incorporation varies in biochemical energy demand. We hypothesized that due to the lesser energy requirement of ammonium ()‐use, in contrast to nitrate ()‐use, more energy remains for other metabolic processes, especially under CO2‐ and phosphorus (Pi) limiting conditions. Therefore, we tested differences in cell characteristics of the green alga Chlamydomonas acidophila grown on or under covariation of CO2 and Pi‐supply in order to determine limitations, in a full‐factorial design. As expected, results revealed higher carbon fixation rates for ‐grown cells compared to growth with under low CO2 conditions. ‐grown cells accumulated more of the nine analyzed amino acids, especially under Pi‐limited conditions, compared to cells provided with . This is probably due to a slower protein synthesis in cells provided with . In contrast to our expectations, compared to ‐grown cells ‐grown cells had higher photosynthetic efficiency under Pi‐limitation. In conclusion, growth on the Ni‐source did not result in a clearly enhanced Ci‐assimilation, as it was highly dependent on Pi and CO2 conditions (replete or limited). Results are potentially connected to the fact that C. acidophila is able to use only CO2 as its inorganic carbon (Ci) source. 相似文献
79.
Nicla Romano Sabrina Ceccariglia Luigi Abelli Massimo Mazzini Lucia Mastrolia 《Polar Biology》2000,23(5):321-328
Lymphomyeloid organs of two common species of Antarctic fish, Trematomus nicolai and Chionodraco hamatus, were studied with the aim of analysing some morphological aspects of these organs in relation to adaptation to low environmental
temperature. The thymuses of T. nicolai and C. hamatus were flattened, incompletely lobated, with numerous Hassall-like bodies, which were mainly located in the central part of
the organ in C. hamatus. In T. nicolai, thymocytes, erythroid and reticular epithelial cells filled the organ. In C. hamatus, the thymocytes intermingled with reticular epithelial cells were often close to groups of melano-macrophages. In both species,
the thymus did not show distinct compartmentalisation; however, the thymocytes had significantly different sizes in the outer
and inner portions of the thymus. The head kidney of both species was completely filled by haematopoietic tissue, highly vascularised
and mainly lymphopoietic in T. nicolai, while both erythropoietic and lymphopoietic in C. hamatus. The spleen appeared mainly erythropoietic in T. nicolai and mainly lymphopoietic in C. hamatus. Solitary melano-macrophages in T. nicolai were close to numerous small vascular ellipsoids where erythroid and lymphoid cells were intermingled without the formation
of red and white pulp areas. In C. hamatus, large lymphoid areas were organised around the capillaries. The possible adaptation of lymphoid organs to the low temperature
of polar water is discussed.
Accepted: 8 November 1999 相似文献
80.
AndreasDavid Brunner Marvin Thielert Catherine Vasilopoulou Constantin Ammar Fabian Coscia Andreas Mund Ole B Hoerning Nicolai Bache Amalia Apalategui Markus Lubeck Sabrina Richter David S Fischer Oliver Raether Melvin A Park Florian Meier Fabian J Theis Matthias Mann 《Molecular systems biology》2022,18(3)