全文获取类型
收费全文 | 1757篇 |
免费 | 183篇 |
出版年
2021年 | 42篇 |
2020年 | 17篇 |
2019年 | 24篇 |
2018年 | 31篇 |
2017年 | 36篇 |
2016年 | 34篇 |
2015年 | 90篇 |
2014年 | 71篇 |
2013年 | 74篇 |
2012年 | 96篇 |
2011年 | 118篇 |
2010年 | 65篇 |
2009年 | 71篇 |
2008年 | 82篇 |
2007年 | 57篇 |
2006年 | 53篇 |
2005年 | 60篇 |
2004年 | 65篇 |
2003年 | 64篇 |
2002年 | 48篇 |
2001年 | 29篇 |
2000年 | 41篇 |
1999年 | 44篇 |
1998年 | 17篇 |
1997年 | 19篇 |
1996年 | 18篇 |
1995年 | 14篇 |
1994年 | 16篇 |
1993年 | 17篇 |
1992年 | 34篇 |
1991年 | 24篇 |
1990年 | 29篇 |
1989年 | 28篇 |
1988年 | 24篇 |
1987年 | 28篇 |
1986年 | 22篇 |
1985年 | 16篇 |
1984年 | 16篇 |
1983年 | 26篇 |
1982年 | 22篇 |
1981年 | 17篇 |
1980年 | 16篇 |
1979年 | 17篇 |
1978年 | 16篇 |
1977年 | 15篇 |
1974年 | 12篇 |
1973年 | 18篇 |
1972年 | 16篇 |
1970年 | 12篇 |
1967年 | 11篇 |
排序方式: 共有1940条查询结果,搜索用时 15 毫秒
81.
Zhiwei Chen Jose H. Pereira Hanbin Liu Huu M. Tran Nathan S. Y. Hsu Dean Dibble Seema Singh Paul D. Adams Rajat Sapra Masood Z. Hadi Blake A. Simmons Kenneth L. Sale 《PloS one》2013,8(11)
Ionic liquid pretreatment of biomass has been shown to greatly reduce the recalcitrance of lignocellulosic biomass, resulting in improved sugar yields after enzymatic saccharification. However, even under these improved saccharification conditions the cost of enzymes still represents a significant proportion of the total cost of producing sugars and ultimately fuels from lignocellulosic biomass. Much of the high cost of enzymes is due to the low catalytic efficiency and stability of lignocellulolytic enzymes, especially cellulases, under conditions that include high temperatures and the presence of residual pretreatment chemicals, such as acids, organic solvents, bases, or ionic liquids. Improving the efficiency of the saccharification process on ionic liquid pretreated biomass will facilitate reduced enzyme loading and cost. Thermophilic cellulases have been shown to be stable and active in ionic liquids but their activity is typically at lower levels. Cel5A_Tma, a thermophilic endoglucanase from Thermotoga maritima, is highly active on cellulosic substrates and is stable in ionic liquid environments. Here, our motivation was to engineer mutants of Cel5A_Tma with higher activity on 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) pretreated biomass. We developed a robotic platform to screen a random mutagenesis library of Cel5A_Tma. Twelve mutants with 25–42% improvement in specific activity on carboxymethyl cellulose and up to 30% improvement on ionic-liquid pretreated switchgrass were successfully isolated and characterized from a library of twenty thousand variants. Interestingly, most of the mutations in the improved variants are located distally to the active site on the protein surface and are not directly involved with substrate binding. 相似文献
82.
83.
Jena R. Hickey Janet Nackoney Nathan P. Nibbelink Stephen Blake Aime Bonyenge Sally Coxe Jef Dupain Maurice Emetshu Takeshi Furuichi Falk Grossmann Patrick Guislain John Hart Chie Hashimoto Bernard Ikembelo Omari Ilambu Bila-Isia Inogwabini Innocent Liengola Albert Lotana Lokasola Alain Lushimba Fiona Maisels Joel Masselink Valentin Mbenzo Norbert Mbangia Mulavwa Pascal Naky Nicolas Mwanza Ndunda Pele Nkumu Valentin Omasombo Gay Edwards Reinartz Robert Rose Tetsuya Sakamaki Samantha Strindberg Hiroyuki Takemoto Ashley Vosper Hjalmar S. Kühl 《Biodiversity and Conservation》2013,22(13-14):3085-3104
Habitat loss and hunting threaten bonobos (Pan paniscus), Endangered (IUCN) great apes endemic to lowland rainforests of the Democratic Republic of Congo. Conservation planning requires a current, data-driven, rangewide map of probable bonobo distribution and an understanding of key attributes of areas used by bonobos. We present a rangewide suitability model for bonobos based on a maximum entropy algorithm in which data associated with locations of bonobo nests helped predict suitable conditions across the species’ entire range. We systematically evaluated available biotic and abiotic factors, including a bonobo-specific forest fragmentation layer (forest edge density), and produced a final model revealing the importance of simple threat-based factors in a data poor environment. We confronted the issue of survey bias in presence-only models and devised a novel evaluation approach applicable to other taxa by comparing models built with data from geographically distinct sub-regions that had higher survey effort. The model’s classification accuracy was high (AUC = 0.82). Distance from agriculture and forest edge density best predicted bonobo occurrence with bonobo nests more likely to occur farther from agriculture and in areas of lower edge density. These results suggest that bonobos either avoid areas of higher human activity, fragmented forests, or both, and that humans reduce the effective habitat of bonobos. The model results contribute to an increased understanding of threats to bonobo populations, as well as help identify priority areas for future surveys and determine core bonobo protection areas. 相似文献
84.
David J. Richard Ryan Lena Thomas Bannister Noel Blake William E. Pierceall Nicole E. Carlson Christina Eberhart Keller Marcel Koenig Yuanjun He Dmitriy Minond Jitendra Mishra Michael Cameron Timothy Spicer Peter Hodder Michael H. Cardone 《Bioorganic & medicinal chemistry》2013,21(21):6642-6649
Anti-apoptotic Bcl-2 family proteins are important oncology therapeutic targets. To date, BH3 mimetics that abrogate anti-apoptotic activity have largely been directed at Bcl-2 and/or Bcl-xL. One observed mechanism of resistance to these inhibitors is increased Mcl-1 levels in cells exposed to such therapeutics. For this reason, and because Mcl-1 is important in the onset of lymphoid, myeloid, and other cancers, it has become a target of great interest. However, small molecule inhibitors displaying potency and selectivity for Mcl-1 are lacking. Identifying such compounds has been challenging due to difficulties in translating the target selectivity observed at the biochemical level to the cellular level. Herein we report the results of an HTS strategy coupled with directed hit optimization. Compounds identified have selective Mcl-1 inhibitory activity with greater than 100-fold reduced affinity for Bcl-xL. The selectivity of these compounds at the cellular level was validated using BH3 profiling, a novel personalized diagnostic approach. This assay provides an important functional biomarker that allows for the characterization of cells based upon their dependencies on various anti-apoptotic Bcl-2 proteins. We demonstrate that cells dependent on Mcl-1 or Bcl-2/Bcl-xL for survival are commensurately responsive to compounds that genuinely target those proteins. The identification of compound 9 with uniquely validated and selective Mcl-1 inhibitory activity provides a valuable tool to those studying the intrinsic apoptosis pathway and highlights an important approach in the development of a first-in-class cancer therapeutic. 相似文献
85.
M.J. Siegert A. Behar M. Bentley D. Blake S. Bowden P. Christoffersen C. Cockell H. Corr D. C. Cullen H. Edwards A. Ellery C. Ellis-Evans G. Griffiths R. Hindmarsh D. A. Hodgson E. King H. Lamb L. Lane K. Makinson M. Mowlem J. Parnell D. A. Pearce J. Priscu A. Rivera M. A. Sephton M. R. Sims A . M. Smith M. Tranter J. L. Wadham G. Wilson J. Woodward 《Reviews in Environmental Science and Biotechnology》2007,6(1-3):161-179
Antarctic subglacial lakes have, over the past few years, been hypothesised to house unique forms of life and hold detailed
sedimentary records of past climate change. Testing this hypothesis requires in situ examinations. The direct measurement
of subglacial lakes has been considered ever since the largest and best-known lake, named Lake Vostok, was identified as having
a deep water-column. The Subglacial Antarctic Lake Environments (SALE) programme, set up by the Scientific Committee on Antarctic
Research (SCAR) to oversee subglacial lakes research, state that prior exploration of smaller lakes would be a “prudent way
forward”. Over 145 subglacial lakes are known to exist in Antarctica, but one lake in West Antarctica, officially named Ellsworth
Subglacial Lake (referred to hereafter as Lake Ellsworth), stands out as a candidate for early exploration. A consortium of
over 20 scientists from seven countries and 14 institutions has been assembled to plan the exploration of Lake Ellsworth.
An eight-year programme is envisaged: 3 years for a geophysical survey, 2 years for equipment development and testing, 1 year
for field planning and operation, and 2 years for sample analysis and data interpretation. The science experiment is simple
in concept but complex in execution. Lake Ellsworth will be accessed using hot water drilling. Once lake access is achieved,
a probe will be lowered down the borehole and into the lake. The probe will contain a series of instruments to measure biological,
chemical and physical characteristics of the lake water and sediments, and will utilise a tether to the ice surface through
which power, communication and data will be transmitted. The probe will pass through the water column to the lake floor. The
probe will then be pulled up and out of the lake, measuring its environment continually as this is done. Once at the ice surface,
any water samples collected will be taken from the probe for laboratory analysis (to take place over subsequent years). The
duration of the science mission, from deployment of the probe to its retrieval, is likely to take between 24 and 36 h. Measurements
to be taken by the probe will provide data about the following: depth, pressure, conductivity and temperature; pH levels;
biomolecules (using life marker chips); anions (using a chemical analyzer); visualisation of the environment (using cameras
and light sources); dissolved gases (using chromatography); and morphology of the lake floor and sediment structures (using
sonar). After the probe has been retrieved, a sediment corer may be dropped into the lake to recover material from the lake
floor. Finally, if time permits, a thermistor string may be left in the lake water to take time-dependent measurements of
the lake’s water column over subsequent years. Given that the comprehensive geophysical survey of the lake will take place
in two seasons during 2007–2009, a two-year instrument and logistic development phase from 2008 (after the lake’s bathymetry
has been assessed) makes it possible that the exploration of Lake Ellsworth could take place at the beginning of the next
decade. 相似文献
86.
Loiselle Bette A.; Ryder Thomas B.; Duraes Renata; Tori Wendy; Blake John G.; Parker Patricia G. 《Behavioral ecology》2007,18(2):287-291
In lek-mating systems, males aggregate at display arenas andfemales visit solely for the purpose of mating. This breedingsystem is characterized by high variance in male mating successwith one male often receiving most copulations. High reproductiveskew among males has led to question why males join leks whentheir chances of reproductive success are so low. Kin selectionhas been invoked as a mechanism to explain the evolution oflekking behavior, whereby nonreproducing but genetically relatedmales gain indirect inclusive-fitness benefits. Evidence forkin selection among lek-mating birds is, however, mixed. Here,we show that kin selection is unlikely to be an important explanationfor evolution of lekking behavior in manakins (Aves: Pipridae).We found that for 4 species chosen from several major cladeswithin Pipridae, males within leks were not significantly morerelated than expected from random assortment of males in thepopulation. This means that nonreproducing males do not gainindirect inclusive-fitness benefits by joining leks. This resultsuggests alternative mechanisms must be invoked to explain theevolution of lek-mating systems in manakins. 相似文献
87.
88.
Current literature related to the impact of probiotics on the incidence of gastrointestinal tract infections (GITIs) has shown mixed results and no systematic review available with pooled analysis exists. Thus, the aim of this systematic review was to provide contemporary evidence regarding the overall and strain-specific influence of probiotics in preventing GITIs among infants and children attending childcare centres. The review shortlisted 18 RCTs after screening through the initial search results of 779 articles. However, only 15 trials were deemed eligible, addressing at least one outcome in the pooled analysis. It is concluded that the supplementation of probiotics (overall effect) may reduce the risk of GITI episode by 26%, with Lacticaseibacillus paracasei, Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus GG being specifically potent probiotic strains in reducing GITI episode, duration of infection and absence from childcare respectively. There is insufficient evidence to determine the effect of Bifidobacterium animalis subsp. lactis BB-12 based on the findings of the trials included in this review. 相似文献
89.
Alptekin Burcu Erfatpour Mohammad Mangel Dylan Pauli Duke Blake Tom Turner Hannah Lachowiec Jennifer Sherman Jamie Fischer Andreas 《Molecular breeding : new strategies in plant improvement》2022,42(10):1-15
Molecular Breeding - Maize amylose is a type of high value-added starch used for medical, food, and chemical applications. Mutations in the starch branching enzyme (SBEIIb), with recessive ae... 相似文献
90.