全文获取类型
收费全文 | 795篇 |
免费 | 109篇 |
出版年
2022年 | 5篇 |
2021年 | 22篇 |
2020年 | 10篇 |
2019年 | 16篇 |
2018年 | 13篇 |
2017年 | 17篇 |
2016年 | 20篇 |
2015年 | 20篇 |
2014年 | 30篇 |
2013年 | 39篇 |
2012年 | 55篇 |
2011年 | 37篇 |
2010年 | 30篇 |
2009年 | 27篇 |
2008年 | 28篇 |
2007年 | 45篇 |
2006年 | 29篇 |
2005年 | 24篇 |
2004年 | 36篇 |
2003年 | 28篇 |
2002年 | 24篇 |
2001年 | 15篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1993年 | 8篇 |
1992年 | 16篇 |
1991年 | 15篇 |
1990年 | 9篇 |
1989年 | 12篇 |
1988年 | 14篇 |
1987年 | 10篇 |
1986年 | 11篇 |
1985年 | 11篇 |
1984年 | 8篇 |
1981年 | 6篇 |
1979年 | 9篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1975年 | 10篇 |
1974年 | 11篇 |
1973年 | 8篇 |
1972年 | 8篇 |
1970年 | 6篇 |
1969年 | 5篇 |
1968年 | 5篇 |
1967年 | 5篇 |
1966年 | 5篇 |
排序方式: 共有904条查询结果,搜索用时 15 毫秒
81.
Staying out in the cold: glacial refugia and mitochondrial DNA phylogeography in ancient European brown bears 总被引:4,自引:1,他引:3
Valdiosera CE García N Anderung C Dalén L Crégut-Bonnoure E Kahlke RD Stiller M Brandström M Thomas MG Arsuaga JL Götherström A Barnes I 《Molecular ecology》2007,16(24):5140-5148
Models for the development of species distribution in Europe typically invoke restriction in three temperate Mediterranean refugia during glaciations, from where recolonization of central and northern Europe occurred. The brown bear, Ursus arctos, is one of the taxa from which this model is derived. Sequence data generated from brown bear fossils show a complex phylogeographical history for western European populations. Long-term isolation in separate refugia is not required to explain our data when considering the palaeontological distribution of brown bears. We propose continuous gene flow across southern Europe, from which brown bear populations expanded after the last glaciation. 相似文献
82.
Vink M Derr K Love J Stokes DL Ubarretxena-Belandia I 《Journal of structural biology》2007,160(3):295-304
Electron microscopy of two-dimensional (2D) crystals has demonstrated potential for structure determination of membrane proteins. Technical limitations in large-scale crystallization screens have, however, prevented a major breakthrough in the routine application of this technology. Dialysis is generally used for detergent removal and reconstitution of the protein into a lipid bilayer, and devices for testing numerous conditions in parallel are not readily available. Furthermore, the small size of resulting 2D crystals requires electron microscopy to evaluate the results and automation of the necessary steps is essential to achieve a reasonable throughput. We have designed a crystallization block, using standard microplate dimensions, by which 96 unique samples can be dialyzed simultaneously against 96 different buffers and have demonstrated that the rate of detergent dialysis is comparable to those obtained with conventional dialysis devices. A liquid-handling robot was employed to set up 2D crystallization trials with the membrane proteins CopA from Archaeoglobus fulgidus and light-harvesting complex II (LH2) from Rhodobacter sphaeroides. For CopA, 1 week of dialysis yielded tubular crystals and, for LH2, large and well-ordered vesicular 2D crystals were obtained after 24 h, illustrating the feasibility of this approach. Combined with a high-throughput procedure for preparation of EM-grids and automation of the subsequent negative staining step, the crystallization block offers a novel pipeline that promises to speed up large-scale screening of 2D crystallization and to increase the likelihood of producing well-ordered crystals for analysis by electron crystallography. 相似文献
83.
Engineered protein libraries, defined here as a collection of different mutant variants of a single specific protein, are intentionally designed to be rich in molecular diversity and can span ranges from as little as 400 different variants to greater than 10(12) members per library. The goal of engineering libraries is to generate new protein variants, identified upon screening, that possess desired novel properties. Exploitation of the natural organization of the genetic code has led to 'focused' libraries that are lower in overall complexity yet biased towards variants with preferred biophysical properties. An emerging trend, in which computational algorithms are blended with in vivo screens, is also leading towards greater and more rapid success in the field of protein design. 相似文献
84.
Love AJ Laval V Geri C Laird J Tomos AD Hooks MA Milner JJ 《Molecular plant-microbe interactions : MPMI》2007,20(6):659-670
We analyzed the susceptibility of Arabidopsis mutants with defects in salicylic acid (SA) and jasmonic acid (JA)/ethylene (ET) signaling to infection by Cauliflower mosaic virus (CaMV). Mutants cpr1-1 and cpr5-2, in which SA-dependent defense signaling is activated constitutively, were substantially more resistant than the wild type to systemic infection, implicating SA signaling in defense against CaMV. However, SA-deficient NahG, sid2-2, eds5-1, and pad4-1 did not show enhanced susceptibility. A cpr5 eds5 double mutant also was resistant, suggesting that resistance in cpr5 may function partially independently of SA. Treatment of cpr5 and cpr5 eds5, but not cpr1, with salicyl-hydroxamic acid, an inhibitor of alternative oxidase, partially restored susceptibility to wild-type levels. Mutants etr1-1, etr1-3, and ein2-1, and two mutants with lesions in ET/JA-mediated defense, eds4 and eds8, also showed reduced virus susceptibility, demonstrating that ET-dependent responses also play a role in susceptibility. We used a green fluorescent protein (GFP)-expressing CaMV recombinant to monitor virus movement. In mutants with reduced susceptibility, cpr1-1, cpr5-2, and etr1-1, CaMV-GFP formed local lesions similar to the wild type, but systemic spread was almost completely absent in cpr1 and cpr5 and was substantially reduced in etr1-1. Thus, mutations with enhanced systemic acquired resistance or compromised ET signaling show diminished long-distance virus movement. 相似文献
85.
T Maisch C Bosl R-M Szeimies B Love C Abels 《Photochemical & photobiological sciences》2007,6(5):545-551
Following extensive in vitro screening of new photosensitizers the purpose of the present study was to examine penetration as well as antibacterial efficacy of a lead photosensitizer against MRSA using an ex vivo porcine skin model. Two different applications were performed: (i) preincubation of bacteria in solution with a porphyrin-based photosensitizer XF73 and subsequent application on the ex vivo porcine skin; (ii) application of pure bacteria on the explants followed by an incubation with XF73 in a water-ethanol formulation for up to 60 min under occlusion. The localisation of XF73 was restricted to the stratum corneum. Different concentrations (0-10 microM) of XF73 and different incubation times (5-60 min) were used to determine phototoxicity against methicillin-resistant and methicillin-sensitive S. aureus, which was applied on the explants. Preincubation of S. aureus with 0.1 microM XF73 in solution prior to the application of these XF73-incubated bacteria on the skin demonstrates a higher efficacy (>3 log10) after irradiation. Antibacterial photodynamic inactivation resulted in a approximately 1 log10 (0.1 microM)-3.64+/-0.035 (10 microM) log10 growth reduction independently of the antibiotic resistance pattern of used S. aureus strains. Irradiation of applied bacteria without photosensitizer incubation did not show any marked decrease (<1 log10) of bacteria cell number, indicating a significant phototoxicity of the XF73. Histological evaluations of untreated and treated skin areas upon irradiation within 24 h showed no significant degree of necrosis or apoptosis determined by TUNEL-assay indicating that the porcine skin is still vital. This study demonstrates that this XF73 porphyrin-based photosensitizer had concentration-dependent differences in killing efficacy of MRSA in comparison to skin cells using an ex vivo porcine skin model. The results described here imply that topical delivery of XF73 may be considered as a possible treatment in patients with superficial infections of the skin. 相似文献
86.
The larval arms of echinoid plutei are used for locomotion and feeding. They are composed of internal calcite skeletal rods covered by an ectoderm layer bearing a ciliary band. Skeletogenesis includes an autonomous molecular differentiation program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal plate for the blastocoel, and a patterning of the differentiated skeletal units that requires molecular cues from the overlaying ectoderm. The arms represent a larval feature that arose in the echinoid lineage during the Paleozoic and offers a subject for the study of gene co-option in the evolution of novel larval features. We isolated new molecular markers in two closely related but differently developing species, Heliocidaris tuberculata and Heliocidaris erythrogramma. We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase. Tetraspanin localizes to the animal half of blastula stage H. tuberculata and then undergoes a restriction into the putative oral ectoderm and future location of the postoral arms, where it continues to be expressed at the leading edge of both the postoral and anterolateral arms. In H. erythrogramma, its expression initiates in the animal half of blastulae and expands over the entire ectoderm from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the PMCs postgastrulation and localized to the leading edge of the growing larval arms of H. tuberculata but do not exhibit coordinated expression in H. erythrogramma larvae. The tight spatiotemporal regulation of these genes in H. tuberculata along with other ontogenetic and phylogenetic evidence suggest that pluteus arms are novel larval organs, distinguishable from the processes of skeletogenesis per se. The dissociation of expression control in H. erythrogramma suggest that coordinate gene expression in H. tuberculata evolved as part of the evolution of pluteus arms, and is not required for larval or adult development. 相似文献
87.
The Oxidative Cost of Acoustic Signals: Examining Steroid Versus Aerobic Activity Hypotheses in a Wild Bird 下载免费PDF全文
Sarah Baldo Daniel J. Mennill Sarah Guindre‐Parker Hugh Grant Gilchrist Oliver P. Love 《Ethology : formerly Zeitschrift fur Tierpsychologie》2015,121(11):1081-1090
Vertebrate vocalizations are widespread secondary sexual signals used for mate attraction and territory defence, and variation in signal quality is often condition dependent and impacts reproductive outcomes. Although vocal signal performance is known to reflect various aspects of male quality, few studies have examined the underlying mechanisms mediating its costs and hence its honesty. Using a population of Arctic‐breeding snow buntings (Plectrophenax nivalis), we compared the ‘Oxidation Handicap Hypothesis’, which predicts that testosterone‐induced increases in oxidative stress provide a direct mechanistic basis for ensuring the honesty of many secondary sexual signals, to the ‘Aerobic Activity Hypothesis, which predicts that it is the aerobic activity involved with signal production (i.e. vocal performance or defending a large territory) and not testosterone directly that links signal quality and oxidative stress. Males singing at faster rates had higher levels of both reactive oxygen metabolites and non‐enzymatic antioxidant capacity in the plasma (i.e. without an increase in overall oxidative stress), enabling certain males to produce high‐quality signals while also mitigating the costs of an associated increase in oxidative stress. However, these results were completely independent of plasma testosterone levels, supporting the role of aerobic performance in directly affecting oxidative stress. Although song performance was not linked to reproductive parameters in our data set, our research is the first to test these competing hypotheses in a behavioural trait and results suggest that oxidative stress may be an underlying physiological cost preventing low‐quality individuals from producing high‐quality signals. 相似文献
88.
P. B. Matheus Carnevali M. Rohrssen M. R. Williams A. B. Michaud H. Adams D. Berisford G. D. Love J. C. Priscu O. Rassuchine K. P. Hand A. E. Murray 《Geobiology》2015,13(2):181-197
The permafrost on the North Slope of Alaska is densely populated by shallow lakes that result from thermokarst erosion. These lakes release methane (CH4) derived from a combination of ancient thermogenic pools and contemporary biogenic production. Despite the potential importance of CH4 as a greenhouse gas, the contribution of biogenic CH4 production in arctic thermokarst lakes in Alaska is not currently well understood. To further advance our knowledge of CH4 dynamics in these lakes, we focused our study on (i) the potential for microbial CH4 production in lake sediments, (ii) the role of sediment geochemistry in controlling biogenic CH4 production, and (iii) the temperature dependence of this process. Sediment cores were collected from one site in Siqlukaq Lake and two sites in Sukok Lake in late October to early November. Analyses of pore water geochemistry, sedimentary organic matter and lipid biomarkers, stable carbon isotopes, results from CH4 production experiments, and copy number of a methanogenic pathway‐specific gene (mcrA) indicated the existence of different sources of CH4 in each of the lakes chosen for the study. Analysis of this integrated data set revealed that there is biological CH4 production in Siqlukaq at moderate levels, while the very low levels of CH4 detected in Sukok had a mixed origin, with little to no biological CH4 production. Furthermore, methanogenic archaea exhibited temperature‐dependent use of in situ substrates for methanogenesis, and the amount of CH4 produced was directly related to the amount of labile organic matter in the sediments. This study constitutes an important first step in better understanding the actual contribution of biogenic CH4 from thermokarst lakes on the coastal plain of Alaska to the current CH4 budgets. 相似文献
89.
Kristin R. Di Bona Sharifa Love Nicholas R. Rhodes DeAna McAdory Sarmistha Halder Sinha Naomi Kern Julia Kent Jessyln Strickland Austin Wilson Janis Beaird James Ramage Jane F. Rasco John B. Vincent 《Journal of biological inorganic chemistry》2011,16(3):381-390
Chromium was proposed to be an essential trace element over 50?years ago and has been accepted as an essential element for over 30?years. However, the studies on which chromium’s status are based are methodologically flawed. Whether chromium is an essential element has been examined for the first time in carefully controlled metal-free conditions using a series of purified diets containing various chromium contents. Male Zucker lean rats were housed in specially designed metal-free cages for 6?months and fed the AIN-93G diet with no added chromium in the mineral mix component of the diet, the standard AIN-93G diet, the standard AIN-93G diet supplemented with 200?μg?Cr/kg, or the standard AIN-93G diet supplemented with 1,000?μg?Cr/kg. The chromium content of the diet had no effect on body mass or food intake. Similarly, the chromium content of the diet had no effect on glucose levels in glucose tolerance or insulin tolerance tests. However, a distinct trend toward lower insulin levels under the curve after a glucose challenge was observed with increasing chromium content in the diet; rats on the supplemented AIN-93G diets had significantly lower areas (P?<?0.05) than rats on the low-chromium diet. The studies reveal that a diet with as little chromium as reasonably possible had no effect on body composition, glucose metabolism, or insulin sensitivity compared with a chromium-“sufficient??diet. Together with the results of other recent studies, these results clearly indicate that chromium can no longer be considered an essential element. 相似文献
90.
NalC is a TetR type regulator that represses the multidrug efflux pump MexAB-OprM in Pseudomonas aeruginosa. Here we explain the mechanism of NalC-mediated regulation of MexAB-OprM. We show that NalC non-covalently binds chlorinated phenols and chemicals containing chlorophenol side-chains such as triclosan. NalC-chlorinated phenol binding results in its dissociation from promoter DNA and upregulation of NalC's downstream targets, including the MexR antirepressor ArmR. ArmR upregulation and MexR-ArmR complex formation have previously been shown to upregulate MexAB-OprM. In vivo mexB and armR expression analyses were used to corroborate in vitro NalC-chlorinated phenol binding. We also show that the interaction between chlorinated phenols and NalC is reversible, such that removal of these chemicals restored NalC promoter DNA binding. Thus, the NalC-chlorinated phenol interaction is likely a pertinent physiological mechanism that P. aeruginosa uses to control expression of the MexAB-OprM efflux pump. 相似文献