全文获取类型
收费全文 | 1429篇 |
免费 | 209篇 |
出版年
2022年 | 12篇 |
2021年 | 23篇 |
2020年 | 18篇 |
2019年 | 18篇 |
2018年 | 15篇 |
2017年 | 15篇 |
2016年 | 20篇 |
2015年 | 49篇 |
2014年 | 38篇 |
2013年 | 64篇 |
2012年 | 75篇 |
2011年 | 64篇 |
2010年 | 67篇 |
2009年 | 48篇 |
2008年 | 64篇 |
2007年 | 67篇 |
2006年 | 58篇 |
2005年 | 73篇 |
2004年 | 62篇 |
2003年 | 68篇 |
2002年 | 54篇 |
2001年 | 41篇 |
2000年 | 36篇 |
1999年 | 31篇 |
1998年 | 15篇 |
1997年 | 10篇 |
1996年 | 15篇 |
1995年 | 16篇 |
1994年 | 18篇 |
1993年 | 18篇 |
1992年 | 26篇 |
1991年 | 16篇 |
1990年 | 23篇 |
1989年 | 29篇 |
1988年 | 27篇 |
1987年 | 25篇 |
1986年 | 23篇 |
1985年 | 28篇 |
1984年 | 21篇 |
1983年 | 15篇 |
1982年 | 12篇 |
1979年 | 14篇 |
1977年 | 10篇 |
1976年 | 9篇 |
1975年 | 12篇 |
1973年 | 11篇 |
1971年 | 15篇 |
1970年 | 14篇 |
1969年 | 11篇 |
1966年 | 8篇 |
排序方式: 共有1638条查询结果,搜索用时 15 毫秒
71.
Kelly O. Maloney Kevin P. Krause Claire Buchanan Lauren E. Hay Gregory J. McCabe Zachary M. Smith Terry L. Sohl John A. Young 《Global Change Biology》2020,26(4):2251-2269
Land‐use and climate change are significantly affecting stream ecosystems, yet understanding of their long‐term impacts is hindered by the few studies that have simultaneously investigated their interaction and high variability among future projections. We modeled possible effects of a suite of 2030, 2060, and 2090 land‐use and climate scenarios on the condition of 70,772 small streams in the Chesapeake Bay watershed, United States. The Chesapeake Basin‐wide Index of Biotic Integrity, a benthic macroinvertebrate multimetric index, was used to represent stream condition. Land‐use scenarios included four Special Report on Emissions Scenarios (A1B, A2, B1, and B2) representing a range of potential landscape futures. Future climate scenarios included quartiles of future climate changes from downscaled Coupled Model Intercomparison Project ‐ Phase 5 (CMIP5) and a watershed‐wide uniform scenario (Lynch2016). We employed random forests analysis to model individual and combined effects of land‐use and climate change on stream conditions. Individual scenarios suggest that by 2090, watershed‐wide conditions may exhibit anywhere from large degradations (e.g., scenarios A1B, A2, and the CMIP5 25th percentile) to small degradations (e.g., scenarios B1, B2, and Lynch2016). Combined land‐use and climate change scenarios highlighted their interaction and predicted, by 2090, watershed‐wide degradation in 16.2% (A2 CMIP5 25th percentile) to 1.0% (B2 Lynch2016) of stream kilometers. A goal for the Chesapeake Bay watershed is to restore 10% of stream kilometers over a 2008 baseline; our results suggest meeting and sustaining this goal until 2090 may require improvement in 11.0%–26.2% of stream kilometers, dependent on land‐use and climate scenario. These results highlight inherent variability among scenarios and the resultant uncertainty of predicted conditions, which reinforces the need to incorporate multiple scenarios of both land‐use (e.g., development, agriculture, etc.) and climate change in future studies to encapsulate the range of potential future conditions. 相似文献
72.
Xue Bessie Su Menglu Wang Claudia Schaffner Olga O. Nerusheva Dean Clift Christos Spanos David A. Kelly Michael Tatham Andreas Wallek Yehui Wu Juri Rappsilber A. Arockia Jeyaprakash Zuzana Storchova Ronald T. Hay Adle L. Marston 《The Journal of cell biology》2021,220(7)
During mitosis, sister chromatids attach to microtubules from opposite poles, called biorientation. Sister chromatid cohesion resists microtubule forces, generating tension, which provides the signal that biorientation has occurred. How tension silences the surveillance pathways that prevent cell cycle progression and correct erroneous kinetochore–microtubule attachments remains unclear. Here we show that SUMOylation dampens error correction to allow stable sister kinetochore biorientation and timely anaphase onset. The Siz1/Siz2 SUMO ligases modify the pericentromere-localized shugoshin (Sgo1) protein before its tension-dependent release from chromatin. Sgo1 SUMOylation reduces its binding to protein phosphatase 2A (PP2A), and weakening of this interaction is important for stable biorientation. Unstable biorientation in SUMO-deficient cells is associated with persistence of the chromosome passenger complex (CPC) at centromeres, and SUMOylation of CPC subunit Bir1 also contributes to timely anaphase onset. We propose that SUMOylation acts in a combinatorial manner to facilitate dismantling of the error correction machinery within pericentromeres and thereby sharpen the metaphase–anaphase transition. 相似文献
73.
Deepali Bhandari Jinzhong Zhang Shekar Menon Christopher Lord Shuliang Chen Jared R. Helm Kevin Thorsen Kevin D. Corbett Jesse C. Hay Susan Ferro-Novick 《Molecular biology of the cell》2013,24(17):2727-2738
Traffic from the endoplasmic reticulum (ER) to the Golgi complex is initiated when the activated form of the GTPase Sar1p recruits the Sec23p-Sec24p complex to ER membranes. The Sec23p-Sec24p complex, which forms the inner shell of the COPII coat, sorts cargo into ER-derived vesicles. The coat inner shell recruits the Sec13p-Sec31p complex, leading to coat polymerization and vesicle budding. Recent studies revealed that the Sec23p subunit sequentially interacts with three different binding partners to direct a COPII vesicle to the Golgi. One of these binding partners is the serine/threonine kinase Hrr25p. Hrr25p phosphorylates the COPII coat, driving the membrane-bound pool into the cytosol. The phosphorylated coat cannot rebind to the ER to initiate a new round of vesicle budding unless it is dephosphorylated. Here we screen all known protein phosphatases in yeast to identify one whose loss of function alters the cellular distribution of COPII coat subunits. This screen identifies the PP2A-like phosphatase Sit4p as a regulator of COPII coat dephosphorylation. Hyperphosphorylated coat subunits accumulate in the sit4Δ mutant in vivo. In vitro, Sit4p dephosphorylates COPII coat subunits. Consistent with a role in coat recycling, Sit4p and its mammalian orthologue, PP6, regulate traffic from the ER to the Golgi complex. 相似文献
74.
Ljudmilla Borisjuk Thomas Neuberger J?rg Schwender Nicolas Heinzel Stephanie Sunderhaus Johannes Fuchs Jordan O. Hay Henning Tschiersch Hans-Peter Braun Peter Denolf Bart Lambert Peter M. Jakob Hardy Rolletschek 《The Plant cell》2013,25(5):1625-1640
Constrained to develop within the seed, the plant embryo must adapt its shape and size to fit the space available. Here, we demonstrate how this adjustment shapes metabolism of photosynthetic embryo. Noninvasive NMR-based imaging of the developing oilseed rape (Brassica napus) seed illustrates that, following embryo bending, gradients in lipid concentration became established. These were correlated with the local photosynthetic electron transport rate and the accumulation of storage products. Experimentally induced changes in embryo morphology and/or light supply altered these gradients and were accompanied by alterations in both proteome and metabolome. Tissue-specific metabolic models predicted that the outer cotyledon and hypocotyl/radicle generate the bulk of plastidic reductant/ATP via photosynthesis, while the inner cotyledon, being enclosed by the outer cotyledon, is forced to grow essentially heterotrophically. Under field-relevant high-light conditions, major contribution of the ribulose-1,5-bisphosphate carboxylase/oxygenase–bypass to seed storage metabolism is predicted for the outer cotyledon and the hypocotyl/radicle only. Differences between in vitro– versus in planta–grown embryos suggest that metabolic heterogeneity of embryo is not observable by in vitro approaches. We conclude that in vivo metabolic fluxes are locally regulated and connected to seed architecture, driving the embryo toward an efficient use of available light and space. 相似文献
75.
76.
Galectins constitute an evolutionary conserved family that bind to β-galactosides. Increasing evidence shows that galectins are involved in many fundamental biological processes such as cellular communication, inflammation, differentiation and apoptosis. Changes in galectin-3 (Gal-3) expression are commonly seen in cancer and pre-cancerous conditions, and Gal-3 may be involved in the regulation of diverse cancer cell activities that contribute to tumourigenesis, cancer progression and metastasis. In addition, Gal-3 is a pro-inflammatory regulator in rheumatoid arthritis. Gal-3 has been shown to be involved in many aspects in allergic inflammation, such as eosinophil recruitment, airway remodeling, development of a Th2 phenotype as well as increased expression of inflammatory mediators. In an in vivo model it was shown that bronchoalveolar lavage (BAL) fluid from ovalbumin-challenged mice contained significantly higher levels of Gal-3 compared to control mice. The molecular mechanisms of Gal-3 in human asthma have not been fully elucidated. This review will focus on what is known about the Gal-3 and its role in the pathophysiological mechanisms of asthma to evaluate the potential of Gal-3 as a biomarker and therapeutic target of asthma. 相似文献
77.
Johanna Aponte-González Luisa Fajardo-Bernal Jorge Diaz Javier Eslava-Schmalbach Oscar Gamboa Joel W. Hay 《PloS one》2013,8(11)
Objective
To compare costs and effectiveness of three strategies used against cervical cancer (CC) and genital warts: (i) Screening for CC; (ii) Bivalent Human Papillomavirus (HPV) 16/18 vaccine added to screening; (iii) Quadrivalent HPV 6/11/16/18 vaccine added to screening.Methods
A Markov model was designed in order to simulate the natural history of the disease from 12 years of age (vaccination) until death. Transition probabilities were selected or adjusted to match the HPV infection profile in Colombia. A systematic review was undertaken in order to derive efficacy values for the two vaccines as well as for the operational characteristics of the cytology test. The societal perspective was used. Effectiveness was measured in number of averted Disability Adjusted Life Years (DALYS).Results
At commercial prices reported for 2010 the two vaccines were shown to be non-cost-effective alternatives when compared with the existing screening strategy. Sensitivity analyses showed that results are affected by the cost of vaccines and their efficacy values, making it difficult to determine with certainty which of the two vaccines has the best cost-effectiveness profile. To be ‘cost-effective’ vaccines should cost between 141 and 147 USD (Unite States Dollars) per vaccinated girl at the most. But at lower prices such as those recommended by WHO or the price of other vaccines in Colombia, HPV vaccination could be considered very cost-effective.Conclusions
HPV vaccination could be a convenient alternative for the prevention of CC in Colombia. However, the price of the vaccine should be lower for this vaccination strategy to be cost-effective. It is also important to take into consideration the willingness to pay, budgetary impact, and program implications, in order to determine the relevance of a vaccination program in this country, as well as which vaccine should be selected for use in the program. 相似文献78.
Jerome Hottin Edy Wijaya Laurent Hay Sophie Maricot Mohamed Bouazaoui Jean-Pierre Vilcot 《Plasmonics (Norwell, Mass.)》2013,8(2):619-624
A large majority of surface plasmon resonance (SPR) sensors reported in the literature are designed to operate in the visible electromagnetic spectrum. However, the near-infrared, particularly at the telecommunications wavelength of 1550 nm, is also especially attractive for SPR sensing applications. In fact, SPR sensors operating in this region benefit from narrower resonance and deeper field penetration. In this paper, we report a theoretical and experimental study of an SPR sensor operating at a fixed wavelength of 1550 nm. The influence of the choice of metals and the interrogation methods on the sensitivity of the resulting SPR sensor is investigated. Two types of sensor chips (simple gold (Au) and bimetallic silver/Au structure) and three interrogation methods (monitoring of the position of the reflectivity minimum, the position of the centroid, and the intensity evolution of the reflectivity) are examined. We show that a refractive index resolution of 2.7?×?10?6 refractive index unit can be easily obtained, and with further optimization of the measurement system, the ultimate limit of detection is expected to be even lowered. Therefore, the approach discussed here already shows a promising potential for highly sensitive SPR sensors. 相似文献
79.
Frédéric B. Piel Simon I. Hay Sunetra Gupta David J. Weatherall Thomas N. Williams 《PLoS medicine》2013,10(7)
Background
The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.Methods and Findings
First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400–398,800) in 2010 to 404,200 (CI: 242,500–657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900–106,100]; 2050: 140,800 [CI: 95,500–200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600–48,800]; 2050: 44,700 [CI: 27,100–70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700–59,100]; 2050: 33,900 [CI: 15,900–64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800–6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800–14,232,700) newborns with SCA globally, 85% (CI: 81%–88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions.Conclusions
Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India. Please see later in the article for the Editors'' Summary 相似文献80.