全文获取类型
收费全文 | 1236篇 |
免费 | 150篇 |
出版年
2021年 | 15篇 |
2019年 | 13篇 |
2018年 | 15篇 |
2017年 | 15篇 |
2016年 | 16篇 |
2015年 | 39篇 |
2014年 | 35篇 |
2013年 | 45篇 |
2012年 | 54篇 |
2011年 | 55篇 |
2010年 | 27篇 |
2009年 | 34篇 |
2008年 | 35篇 |
2007年 | 45篇 |
2006年 | 51篇 |
2005年 | 27篇 |
2004年 | 53篇 |
2003年 | 37篇 |
2002年 | 32篇 |
2001年 | 41篇 |
2000年 | 44篇 |
1999年 | 34篇 |
1998年 | 16篇 |
1996年 | 15篇 |
1994年 | 9篇 |
1993年 | 10篇 |
1992年 | 31篇 |
1991年 | 32篇 |
1990年 | 14篇 |
1989年 | 16篇 |
1988年 | 23篇 |
1987年 | 35篇 |
1986年 | 21篇 |
1985年 | 21篇 |
1984年 | 35篇 |
1983年 | 22篇 |
1982年 | 15篇 |
1981年 | 21篇 |
1980年 | 12篇 |
1979年 | 22篇 |
1978年 | 22篇 |
1977年 | 31篇 |
1976年 | 16篇 |
1975年 | 17篇 |
1974年 | 24篇 |
1973年 | 17篇 |
1972年 | 13篇 |
1971年 | 10篇 |
1970年 | 11篇 |
1969年 | 10篇 |
排序方式: 共有1386条查询结果,搜索用时 984 毫秒
131.
Saito EK Sileo L Green DE Meteyer CU McLaughlin GS Converse KA Docherty DE 《Journal of wildlife diseases》2007,43(2):206-213
West Nile virus (WNV) has affected many thousands of birds since it was first detected in North America in 1999, but the overall impact on wild bird populations is unknown. In mid-August 2002, wildlife rehabilitators and local wildlife officials from multiple states began reporting increasing numbers of sick and dying raptors, mostly red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus). Commonly reported clinical signs were nonspecific and included emaciation, lethargy, weakness, inability to perch, fly or stand, and nonresponse to danger. Raptor carcasses from 12 states were received, and diagnostic evaluation of 56 raptors implicated WNV infection in 40 (71%) of these cases. Histologically, nonsuppurative encephalitis and myocarditis were the salient lesions (79% and 61%, respectively). Other causes of death included lead poisoning, trauma, aspergillosis, and Salmonella spp. and Clostridium spp. infections. The reason(s) for the reported increase in raptor mortality due to WNV in 2002 compared with the previous WNV seasons is unclear, and a better understanding of the epizootiology and pathogenesis of the virus in raptor populations is needed. 相似文献
132.
Interactive effects of ozone and climate on tree growth and water use in a southern Appalachian forest in the USA 总被引:1,自引:0,他引:1
* A lack of data on responses of mature tree growth and water use to ambient ozone (O(3)) concentrations has been a major limitation in efforts to understand and model responses of forests to current and future changes in climate. * Here, hourly to seasonal patterns of stem growth and sap flow velocity were examined in mature trees from a mixed deciduous forest in eastern Tennessee (USA) to evaluate the effects of variations in ambient O(3) exposure and climate on patterns of stem growth and water use. * Ambient O(3) caused a periodic slowdown in seasonal growth patterns that was attributable in part to amplification of diurnal patterns of water loss in tree stems. This response was mediated by statistically significant increases in O(3)-induced daily sap flow and led to seasonal losses in stem growth of 30-50% for most species in a high-O(3) year. * Decreased growth and increased water use of mature forest trees under episodically high ambient O(3) concentrations suggest that O(3) will amplify the adverse effects of increasing temperatures on forest growth and forest hydrology. 相似文献
133.
Haynes KF McLaughlin J Stamper S Rucker C Webster FX Czokajlo D Kirsch P 《Environmental entomology》2007,36(5):1199-1205
The discovery that the eastern tent caterpillar Malacosoma americanum (F.) causes mare reproductive loss syndrome (MRLS), and thus has the potential to continue to result in major economic losses to the equine industry of Kentucky, has resulted in an intensive effort to identify practical means to monitor and control this defoliator, including these experiments to optimize a sex pheromone trap for this pest. A pheromone-baited delta trap with a large opening, such as InterceptST Delta, was more effective than other tested traps. Orange delta traps caught more moths than other tested colors. ETC males are caught at all tested heights within the tree canopy. For monitoring flights, setting traps at 1.5 m would allow easy counting of moths. A 9:1 blend of (E,Z)-5,7-dodecadienal (ETC-Ald) and (E,Z)-5,7-dodecadienol (ETC-OH) was most effective in capturing males. Increasing loading doses of a 3:1 blend (Ald:OH) resulted in the capture of increasing numbers of moths, but a 9:1 blend was more effective than 3:1 blend even at a nine-fold lower loading rate. Pheromone-impregnated white septa caught more moths than gray septa at the same loading dose. The advantages and limitations of using pheromone traps for monitoring M. americanum are discussed. 相似文献
134.
Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs 总被引:1,自引:0,他引:1
Phillips JJ Yao ZP Zhang W McLaughlin S Laue ED Robinson CV Jackson SE 《Journal of molecular biology》2007,372(5):1189-1203
The molecular chaperone Hsp90 is essential for the correct folding, maturation and activation of a diverse array of client proteins, including several key constituents of oncogenic processes. Hsp90 has become a focus of cancer research, since it represents a target for direct prophylaxis against multistep malignancy. Hydrogen-exchange mass spectrometry was used to study the structural and conformational changes undergone by full-length human Hsp90beta in solution upon binding of the kinase-specific co-chaperone Cdc37 and two Hsp90 ATPase inhibitors: Radicicol and the first-generation anticancer drug DMAG. Changes in hydrogen exchange pattern in the complexes in regions of Hsp90 remote to the ligand-binding site were observed indicating long-range effects. In particular, the interface between the N-terminal domain and middle domains exhibited significant differences between the apo and complexed forms. For the inhibitors, differences in the interface between the middle domain and the C-terminal domain were also observed. These data provide important insight into the structure of the biologically active form of the protein. 相似文献
135.
Mutation in HSF4 associated with early but not late-onset hereditary cataract in the Boston Terrier 总被引:1,自引:0,他引:1
Mellersh CS Graves KT McLaughlin B Ennis RB Pettitt L Vaudin M Barnett KC 《The Journal of heredity》2007,98(5):531-533
Primary hereditary cataract (HC) is one of the most common disorders in purebred dogs and is a leading cause of blindness. Boston Terriers suffer from 2 distinct forms of HC which occur at different ages and which are different in their appearance and progression. Early-onset hereditary cataract (EHC) affects dogs within the first few months of life, is always progressive and bilateral, and results in total blindness, whereas late-onset hereditary cataract (LHC) in general affects dogs over the age of 3 and is more variable in its clinical phenotype, age of onset, progression, and the degree to which vision is impaired. A mutation in HSF4 has recently been reported in a small number of Boston Terriers affected with EHC. In this study, we analyzed 22 additional Boston Terriers affected with early-onset cataract to confirm that the HSF4 mutation is causative for this form of cataract in this breed. In addition, we analyzed 40 Boston Terriers that were either clinically clear or affected with LHC for the presence or absence of the HSF4 mutation. By also sequencing HSF4 in dogs affected with LHC, we conclude that HSF4 is not associated with the development of the late-onset form of cataract and that the 2 forms of cataract in this breed are therefore genetically discrete conditions. 相似文献
136.
Pruitt JR Batt DG Wacker DA Bostrom LL Booker SK McLaughlin E Houghton GC Varnes JG Christ DD Covington M Das AM Davies P Graden D Kariv I Orlovsky Y Stowell NC Vaddi KG Wadman EA Welch PK Yeleswaram S Solomon KA Newton RC Decicco CP Carter PH Ko SS 《Bioorganic & medicinal chemistry letters》2007,17(11):2992-2997
DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2D6 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. 相似文献
137.
Feng Z Mohapatra S Klimko PG Hellberg MR May JA Kelly C Williams G McLaughlin MA Sharif NA 《Bioorganic & medicinal chemistry letters》2007,17(11):2998-3002
A series of 8-substituted benzodifuran analogs was prepared and evaluated for 5-HT(2A) receptor binding and activation. Several compounds containing ether and ester functionality were found to be potent agonists. Topical ocular administration of 5, 18, and 25 effectively reduced intra-ocular pressure in the hypertensive cynomolgus monkey eye in the range of 25-37%. 相似文献
138.
A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres 总被引:1,自引:0,他引:1
Dunleavy EM Pidoux AL Monet M Bonilla C Richardson W Hamilton GL Ekwall K McLaughlin PJ Allshire RC 《Molecular cell》2007,28(6):1029-1044
A defining feature of centromeres is the presence of the histone H3 variant CENP-A(Cnp1). It is not known how CENP-A(Cnp1) is specifically delivered to, and assembled into, centromeric chromatin. Through a screen for factors involved in kinetochore integrity in fission yeast, we identified Sim3. Sim3 is homologous to known histone binding proteins NASP(Human) and N1/N2(Xenopus) and aligns with Hif1(S. cerevisiae), defining the SHNi-TPR family. Sim3 is distributed throughout the nucleoplasm, yet it associates with CENP-A(Cnp1) and also binds H3. Cells defective in Sim3 function have reduced levels of CENP-A(Cnp1) at centromeres (and increased H3) and display chromosome segregation defects. Sim3 is required to allow newly synthesized CENP-A(Cnp1) to accumulate at centromeres in S and G2 phase-arrested cells in a replication-independent mechanism. We propose that one function of Sim3 is to act as an escort that hands off CENP-A(Cnp1) to chromatin assembly factors, allowing its incorporation into centromeric chromatin. 相似文献
139.
Annemarie MM Vlaar Angela EP Bouwmans Marinus JPG van Kroonenburgh Werner H Mess Selma C Tromp Piet GWM Wuisman Alfons GH Kessels Ania Winogrodzka Wim EJ Weber 《BMC neurology》2007,7(1):28
Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD. 相似文献140.
Paulo FP Pimenta Alessandra S Orfano Ana C Bahia Ana PM Duarte Claudia M Ríos-Velásquez Fabrício F Melo Felipe AC Pessoa Giselle A Oliveira Keillen MM Campos Luis Martínez Villegas Nilton Barnabé Rodrigues Rafael Nacif-Pimenta Rejane C Sim?es Wuelton M Monteiro Rogerio Amino Yara M Traub-Cseko José BP Lima Maria GV Barbosa Marcus VG Lacerda Wanderli P Tadei Nágila FC Secundino 《Memórias do Instituto Oswaldo Cruz》2015,110(1):23-47
In the Americas, areas with a high risk of malaria transmission are mainly located in
the Amazon Forest, which extends across nine countries. One keystone step to
understanding the Plasmodium life cycle in Anopheles species from the Amazon Region
is to obtain experimentally infected mosquito vectors. Several attempts to colonise
Ano- pheles species have been conducted, but with only short-lived success or no
success at all. In this review, we review the literature on malaria transmission from
the perspective of its Amazon vectors. Currently, it is possible to develop
experimental Plasmodium vivax infection of the colonised and field-captured vectors
in laboratories located close to Amazonian endemic areas. We are also reviewing
studies related to the immune response to P. vivax infection of Anopheles aquasalis,
a coastal mosquito species. Finally, we discuss the importance of the modulation of
Plasmodium infection by the vector microbiota and also consider the anopheline
genomes. The establishment of experimental mosquito infections with Plasmodium
falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide
interesting models for studying malaria in the Amazonian scenario is important.
Understanding the molecular mechanisms involved in the development of the parasites
in New World vectors is crucial in order to better determine the interaction process
and vectorial competence. 相似文献