全文获取类型
收费全文 | 9631篇 |
免费 | 837篇 |
国内免费 | 1篇 |
专业分类
10469篇 |
出版年
2024年 | 12篇 |
2023年 | 41篇 |
2022年 | 113篇 |
2021年 | 234篇 |
2020年 | 116篇 |
2019年 | 158篇 |
2018年 | 192篇 |
2017年 | 168篇 |
2016年 | 305篇 |
2015年 | 491篇 |
2014年 | 517篇 |
2013年 | 566篇 |
2012年 | 799篇 |
2011年 | 766篇 |
2010年 | 475篇 |
2009年 | 439篇 |
2008年 | 586篇 |
2007年 | 601篇 |
2006年 | 546篇 |
2005年 | 548篇 |
2004年 | 508篇 |
2003年 | 479篇 |
2002年 | 446篇 |
2001年 | 94篇 |
2000年 | 66篇 |
1999年 | 116篇 |
1998年 | 117篇 |
1997年 | 77篇 |
1996年 | 65篇 |
1995年 | 60篇 |
1994年 | 57篇 |
1993年 | 60篇 |
1992年 | 68篇 |
1991年 | 51篇 |
1990年 | 56篇 |
1989年 | 36篇 |
1988年 | 39篇 |
1987年 | 38篇 |
1986年 | 30篇 |
1985年 | 25篇 |
1984年 | 27篇 |
1983年 | 17篇 |
1982年 | 27篇 |
1981年 | 21篇 |
1978年 | 13篇 |
1974年 | 18篇 |
1972年 | 15篇 |
1971年 | 15篇 |
1969年 | 11篇 |
1967年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
SUMMARY 1. Field and laboratory experiments were conducted to assess the relative influence of water quality and substratum quality on benthic macroinvertebrate communities in the Animas River, a metal-polluted stream in south-western Colorado (U.S.A.).
2. A community-level in situ toxicity test measured direct effects of Animas River water on benthic invertebrates collected from a reference stream (Elk Creek). The effects of metal-contaminated biofilm were examined by comparing macroinvertebrate colonisation of clean and contaminated substrata placed in Elk Creek. A feeding experiment with the mayfly Baetis tricaudatus Dodds (Ephemeroptera: Baetidae) examined metal bioaccumulation and effects of metal-contaminated biofilm on growth and survival.
3. Animas River water was acutely toxic to most taxa, with greatest effects observed on mayflies (Heptageniidae, Ephemerellidae) and stoneflies (Taeniopterygidae and Capniidae).
4. Although Animas River biofilm was characterised by high concentrations of metals and low algal biomass, most taxa colonised substratum from the reference stream and the Animas River equally. The exceptions were Ephemerellidae, Taeniopterygidae and Simuliidae, which were less abundant on Animas River substratum. Mayflies grazing Animas River biofilm accumulated significantly more metals and showed reduced growth compared with organisms feeding on Elk Creek biofilm.
5. Results of our experiments demonstrated that effects of heavy metals on benthic community structure in the Animas River were complex, and that responses to metals in water and contaminated substratum were species-specific. Predicting recovery of benthic communities following remediation requires an understanding of these species-specific responses. 相似文献
2. A community-level in situ toxicity test measured direct effects of Animas River water on benthic invertebrates collected from a reference stream (Elk Creek). The effects of metal-contaminated biofilm were examined by comparing macroinvertebrate colonisation of clean and contaminated substrata placed in Elk Creek. A feeding experiment with the mayfly Baetis tricaudatus Dodds (Ephemeroptera: Baetidae) examined metal bioaccumulation and effects of metal-contaminated biofilm on growth and survival.
3. Animas River water was acutely toxic to most taxa, with greatest effects observed on mayflies (Heptageniidae, Ephemerellidae) and stoneflies (Taeniopterygidae and Capniidae).
4. Although Animas River biofilm was characterised by high concentrations of metals and low algal biomass, most taxa colonised substratum from the reference stream and the Animas River equally. The exceptions were Ephemerellidae, Taeniopterygidae and Simuliidae, which were less abundant on Animas River substratum. Mayflies grazing Animas River biofilm accumulated significantly more metals and showed reduced growth compared with organisms feeding on Elk Creek biofilm.
5. Results of our experiments demonstrated that effects of heavy metals on benthic community structure in the Animas River were complex, and that responses to metals in water and contaminated substratum were species-specific. Predicting recovery of benthic communities following remediation requires an understanding of these species-specific responses. 相似文献
962.
963.
The effects of simulated aboveground herbivory and phosphate addition to soil on rhizosphere organisms (arbuscular mychorrhiza (AM), Rhizobium spp., bacteria, protozoa and nematodes) were studied in a 2 by 2 factorial designed pot experiment with Pea plants (Pisum sativum). Measurements were performed on 24 day old plants that were still in the nutrient acquisition phase before flowering. AM colonization and bacterial feeding nematodes were stimulated by high simulated her- bivory especially when plants were phosphate deficient. Total number of nematodes was higher with phosphate deficiency. Furthermore, non-significant peak values in soil respiration, total number of nematodes, and bacterial number were observed in phosphate deficient plants with high simulated herbivory. In phosphate amended plants, fast-growing protozoa and bacterial feeding nematodes decreased at high simulated herbivory. These results support the hypothesis that the plant regulates abundances of both AM and free-living rhizosphere organisms and thereby the amount of plant-available nutrients, according to demand via root exudation. Rhizobium spp. was significantly stimulated by phosphate addition but not affected by simulated herbivory. Metabolites produced by rhizosphere bacteria from plants exposed to high simulated herbivory in phosphate amended soil stimulated seed performance. Possible interactions between protozoa and nematodes in relation to production and composition of bacteria in the rhizosphere are discussed. 相似文献
964.
Hung-Hsin Chen Douglas M. Shaw Lauren E. Petty Misa Graff Ryan J. Bohlender Hannah G. Polikowsky Xue Zhong Daeeun Kim Victoria L. Buchanan Michael H. Preuss Megan M. Shuey Ruth J.F. Loos Chad D. Huff Nancy J. Cox Julie A. Bastarache Lisa Bastarache Kari E. North Jennifer E. Below 《American journal of human genetics》2021,108(1):194-201
965.
Examination of the Kinetics of Herpes Simplex Virus Glycoprotein D Binding to the Herpesvirus Entry Mediator, Using Surface Plasmon Resonance 总被引:4,自引:8,他引:4 下载免费PDF全文
Sharon H. Willis Ann H. Rux Charline Peng J. Charles Whitbeck Anthony V. Nicola Huan Lou Wangfang Hou Lisa Salvador Roselyn J. Eisenberg Gary H. Cohen 《Journal of virology》1998,72(7):5937-5947
Previously, we showed that truncated soluble forms of herpes simplex virus (HSV) glycoprotein D (gDt) bound directly to a truncated soluble form of the herpesvirus entry mediator (HveAt, formerly HVEMt), a cellular receptor for HSV. The purpose of the present study was to determine the affinity of gDt for HveAt by surface plasmon resonance and to compare and contrast the kinetics of an expanded panel of gDt variants in binding to HveAt in an effort to better understand the mechanism of receptor binding and virus entry. Both HveAt and gDt are dimers in solution and interact with a 2:1 stoichiometry. With HveAt, gD1(306t) (from the KOS strain of HSV-1) had a dissociation constant (KD) of 3.2 × 10−6 M and gD2(306t) had a KD of 1.5 × 10−6 M. The interaction between gDt and HveAt fits a 1:1 Langmuir binding model, i.e., two dimers of HveAt may act as one binding unit to interact with one dimer of gDt as the second binding unit. A gD variant lacking all signals for N-linked oligosaccharides had an affinity for HveAt similar to that of gD1(306t). A variant lacking the bond from cysteine 1 to cysteine 5 had an affinity for HveAt that did not differ from that of the wild type. However, variants with double cysteine mutations that eliminated either of the other two disulfide bonds showed decreased affinity for HveAt. This result suggests that two of the three disulfide bonds of gD are important for receptor binding. Four nonfunctional gDt variants, each representing one functional domain of gD, were also studied. Mutations in functional regions I and II drastically decreased the affinity of gDt for HveAt. Surprisingly, a variant with an insertion in functional region III had a wild-type level of affinity for HveAt, suggesting that this domain may function in virus entry at a step other than receptor binding. A variant with a deletion in functional region IV [gD1(Δ290-299t)] exhibited a 100-fold enhancement in affinity for HveAt (KD = 3.3 × 10−8 M) due mainly to a 40-fold increase in its kinetic on rate. This agrees with the results of other studies showing the enhanced ability of gD1(Δ290-299t) to block infection. Interestingly, all the variants with decreased affinities for HveAt exhibited decreased kinetic on rates but only minor changes in their kinetic off rates. The results suggest that once the complex between gDt and HveAt forms, its stability is unaffected by a variety of changes in gD. 相似文献
966.
Li Q Claiborne A Li T Hasvold L Stoll VS Muchmore S Jakob CG Gu W Cohen J Hutchins C Frost D Rosenberg SH Sham HL 《Bioorganic & medicinal chemistry letters》2004,14(21):5367-5370
As a part of our efforts to identify potent inhibitors of farnesyltransferase (FTase), modification of the structure of tipifarnib through structure-based design was undertaken by replacing the 2-quinolones with 4-quinolones and pyridones, and subsequent relocation of the D-ring to the N-methyl group on the imidazole ring. This study has yielded a novel series of potent and selective FTase inhibitors. The X-ray structure of tipifarnib (1) in complex with FTase was described. 相似文献
967.
Nanoporous surfaces as harvesting agents for mass spectrometric analysis of peptides in human plasma
Gaspari M Ming-Cheng Cheng M Terracciano R Liu X Nijdam AJ Vaccari L di Fabrizio E Petricoin EF Liotta LA Cuda G Venuta S Ferrari M 《Journal of proteome research》2006,5(5):1261-1266
Silica-based nanoporous surfaces have been developed in order to capture low molecular weight peptides from human plasma. Harvested peptides were subjected to mass spectrometric analysis by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a means of detecting and assessing the bound molecules. Peptide profiles consisting of about 70 peaks in the range 800-10,000 m/z were generated. The method could allow detection of small peptides at ng/mL concentration levels, either in standard solutions or in plasma. The same molecular cutoff effect was observed for mixtures of standard proteins and peptides incubated with silicon-based nanoporous surfaces. 相似文献
968.
Gatzeva-Topalova PZ Warner LR Pardi A Sousa MC 《Structure (London, England : 1993)》2010,18(11):1492-1501
Folding and insertion of β-barrel outer membrane proteins (OMPs) is essential for Gram-negative bacteria. This process is mediated by the multiprotein complex BAM, composed of the essential β-barrel OMP BamA and four lipoproteins (BamBCDE). The periplasmic domain of BamA is key for its function and contains five "polypeptide transport-associated" (POTRA) repeats. Here, we report the crystal structure of the POTRA4-5 tandem, containing the essential for BAM complex formation and cell viability POTRA5. The domain orientation observed in the crystal is validated by solution NMR and SAXS. Using previously determined structures of BamA POTRA1-4, we present a spliced model of the entire BamA periplasmic domain validated by SAXS. Solution scattering shows that conformational flexibility between POTRA2 and 3 gives rise to compact and extended conformations. The length of BamA in its extended conformation suggests that the protein may bridge the inner and outer membranes across the periplasmic space. 相似文献
969.
Prion protein expression differences in microglia and astroglia influence scrapie-induced neurodegeneration in the retina and brain of transgenic mice 下载免费PDF全文
Activated microglia and astroglia are known to be involved in a variety of neurodegenerative diseases, including prion diseases. In the present experiments, we studied activation of astroglia and microglia after intraocular scrapie infection in transgenic mice expressing prion protein (PrP) in multiple cell types (tg7 mice) or in neurons only (tgNSE mice). In this model, scrapie infection and protease-resistant PrP deposition occurs in the retinas of both strains of mice, but retinal degeneration is observed only in tg7 mice. Our results showed that the retinas of tg7 and tgNSE mice both had astroglial activation with increased chemokine expression during the course of infection. However, only tg7 retinas exhibited strong microglial activation compared to tgNSE retinas, which showed little microglial activation by biochemical or morphological criteria. Therefore, microglial PrP expression might be required for scrapie-induced retinal microglial activation and damage. Furthermore, microglial activation preceded retinal neurodegeneration in tg7 mice, suggesting that activated microglia might contribute to the degenerative process, rather than being a response to the damage. Surprisingly, brain differed from retina in that an altered profile of microglial activation markers was upregulated, and the profiles in the two mouse strains were indistinguishable. Microglial activation in the brain was associated with severe brain vacuolation and neurodegeneration, leading to death. Thus, retinal and brain microglia appeared to differ in their requirements for activation, suggesting that different activation pathways occur in the two tissues. 相似文献
970.
Prosser LA Lavelle TA Fiore AE Bridges CB Reed C Jain S Dunham KM Meltzer MI 《PloS one》2011,6(7):e22308