全文获取类型
收费全文 | 3518篇 |
免费 | 340篇 |
国内免费 | 1篇 |
出版年
2024年 | 5篇 |
2023年 | 11篇 |
2022年 | 52篇 |
2021年 | 82篇 |
2020年 | 52篇 |
2019年 | 45篇 |
2018年 | 81篇 |
2017年 | 78篇 |
2016年 | 126篇 |
2015年 | 226篇 |
2014年 | 224篇 |
2013年 | 258篇 |
2012年 | 318篇 |
2011年 | 339篇 |
2010年 | 217篇 |
2009年 | 179篇 |
2008年 | 250篇 |
2007年 | 257篇 |
2006年 | 233篇 |
2005年 | 163篇 |
2004年 | 155篇 |
2003年 | 157篇 |
2002年 | 137篇 |
2001年 | 20篇 |
2000年 | 12篇 |
1999年 | 28篇 |
1998年 | 25篇 |
1997年 | 15篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 8篇 |
1993年 | 8篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
1938年 | 1篇 |
排序方式: 共有3859条查询结果,搜索用时 125 毫秒
911.
Melanie Ann Sacco Kamila Koropacka Eric Grenier Marianne J. Jaubert Alexandra Blanchard Aska Goverse Geert Smant Peter Moffett 《PLoS pathogens》2009,5(8)
Plant NB-LRR proteins confer robust protection against microbes and metazoan
parasites by recognizing pathogen-derived avirulence (Avr) proteins that are
delivered to the host cytoplasm. Microbial Avr proteins usually function as
virulence factors in compatible interactions; however, little is known about the
types of metazoan proteins recognized by NB-LRR proteins and their relationship
with virulence. In this report, we demonstrate that the secreted protein RBP-1
from the potato cyst nematode Globodera pallida elicits defense
responses, including cell death typical of a hypersensitive response (HR),
through the NB-LRR protein Gpa2. Gp-Rbp-1 variants from
G. pallida populations both virulent and avirulent to
Gpa2 demonstrated a high degree of polymorphism, with
positive selection detected at numerous sites. All Gp-RBP-1
protein variants from an avirulent population were recognized by Gpa2, whereas
virulent populations possessed Gp-RBP-1 protein variants both
recognized and non-recognized by Gpa2. Recognition of Gp-RBP-1
by Gpa2 correlated to a single amino acid polymorphism at position 187 in the
Gp-RBP-1 SPRY domain. Gp-RBP-1 expressed
from Potato virus X elicited Gpa2-mediated defenses that required Ran
GTPase-activating protein 2 (RanGAP2), a protein known to interact with the Gpa2
N terminus. Tethering RanGAP2 and Gp-RBP-1 variants via fusion
proteins resulted in an enhancement of Gpa2-mediated responses. However,
activation of Gpa2 was still dependent on the recognition specificity conferred
by amino acid 187 and the Gpa2 LRR domain. These results suggest a two-tiered
process wherein RanGAP2 mediates an initial interaction with pathogen-delivered
Gp-RBP-1 proteins but where the Gpa2 LRR determines which
of these interactions will be productive. 相似文献
912.
Dominik Schüßler Marina B. Blanco Nicola K. Guthrie Gabriele M. Sgarlata Melanie Dammhahn Refaly Ernest Mamy Rina Evasoa Alida Hasiniaina Daniel Hending Fabien Jan Barbara le Pors Alex Miller Gillian Olivieri Ando N. Rakotonanahary Solofomalala Jacques Rakotondranary Romule Rakotondravony Tantely Ralantoharijaona Veronarindra Ramananjato Blanchard Randrianambinina Nancia N. Raoelinjanakolona Emilienne Rasoazanabary Rodin M. Rasoloarison David W. Rasolofoson Solofonirina Rasoloharijaona Emmanuel Rasolondraibe Sam Hyde Roberts Helena Teixeira Tobias van Elst Steig E. Johnson Jörg U. Ganzhorn Lounès Chikhi Peter M. Kappeler Edward E. Louis Jr. Jordi Salmona Ute Radespiel 《American journal of physical anthropology》2024,183(1):60-78
913.
Himpsl SD Pearson MM Arewång CJ Nusca TD Sherman DH Mobley HL 《Molecular microbiology》2010,78(1):138-157
Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an iron-limiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes (P ≤ 0.05) that represent 21 putative iron-regulated systems. Two gene clusters, PMI0229-0239 and PMI2596-2605, encode putative siderophore systems. PMI0229-0239 encodes a non-ribosomal peptide synthetase-independent siderophore system for producing a novel siderophore, proteobactin. PMI2596-2605 are contained within the high-pathogenicity island, originally described in Yersinia pestis, and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross-feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin-related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron-chelating defect; demonstrating production and iron-chelating activity for both siderophores. These findings clearly show that proteobactin and the yersiniabactin-related siderophore function as iron acquisition systems. Despite the activity of both siderophores, only mutants lacking the yersiniabactin-related siderophore have reduced fitness in vivo. The fitness requirement for the yersiniabactin-related siderophore during UTI shows, for the first time, the importance of siderophore production in vivo for P. mirabilis. 相似文献
914.
Melanie Falb Irene Amata Frank Gabel Bernd Simon Teresa Carlomagno 《Nucleic acids research》2010,38(18):6274-6285
K-turn motifs are universal RNA structural elements providing a binding platform for proteins in several cellular contexts. Their characteristic is a sharp kink in the phosphate backbone that puts the two helical stems of the protein-bound RNA at an angle of 60°. However, to date no high-resolution structure of a naked K-turn motif is available. Here, we present the first structural investigation at atomic resolution of an unbound K-turn RNA (the spliceosomal U4-Kt RNA) by a combination of NMR and small-angle neutron scattering data. With this study, we wish to address the question whether the K-turn structural motif assumes the sharply kinked conformation in the absence of protein binders and divalent cations. Previous studies have addressed this question by fluorescence resonance energy transfer, biochemical assays and molecular dynamics simulations, suggesting that the K-turn RNAs exist in equilibrium between a kinked conformation, which is competent for protein binding, and a more extended conformation, with the population distribution depending on the concentration of divalent cations. Our data shows that the U4-Kt RNA predominantly assumes the more extended conformation in the absence of proteins and divalent cations. The internal loop region is well structured but adopts a different conformation from the one observed in complex with proteins. Our data suggests that the K-turn consensus sequence does not per se code for the kinked conformation; instead the sharp backbone kink requires to be stabilized by protein binders. 相似文献
915.
Manuela Nowotny Jennifer Hummel Melanie Weber Doreen Möckel Manfred Kössl 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(12):939-945
Bushcrickets have a tonotopically organised hearing organ, the so-called crista acustica, in the tibia of the forelegs. This organ responds to a frequency range of about 5–80 kHz and lies behind the anterior tympanum
on top of a trachea branch. We analyzed the sound-induced vibration pattern of the anterior tympanum, using a Laser-Doppler-Vibrometer
Scanning microscope system, in order to identify frequency-dependent amplitude and phase of displacement. The vibration pattern
evoked by a frequency sweep (4–79 kHz) showed an amplitude maximum which would correspond to the resonance frequency of an
open tube system. At higher frequencies of about 30 kHz a difference in the amplitude and phase response between the distal
and the proximal part of the tympanum was detected. The inner plate of the tympanum starts to wobble at this frequency. This
higher mode in the motion pattern is not explained by purely acoustic characteristics of the tracheal space below the tympanum
but may depend on the mechanical impedance of the tympanum plate. In accordance with a previous hypothesis, the tympanum moves
over the whole tested frequency range in the dorso-ventral direction like a hinged flap with the largest displacement in its
ventral part and no higher modes of vibration. 相似文献
916.
Ontogenetic change in the visual acuity of Seriola lalandi larvae was measured using both behavioural and anatomical techniques. Visual acuity improved over early development (day
4 to day 7 post-hatch), although for all three larval ages examined estimates of anatomical acuity were consistently lower
(higher acuity) than estimates of behavioural acuity. At hatching the eyes of larval kingfish were characterized by an undifferentiated
retina surrounding a spherical lens, by day 4 post-hatch the eyes appeared to be functional, the retina was fully pigmented
and the optic nerve had made contact with the optic tectum. Analysis of prey search behaviour indicated that larvae employ
a saltatory type search behaviour in which brief stationary periods are interspersed with repositioning movements. The mean
reactive angle increased between day 4 and day 7 post-hatch indicating that the horizontal visual field was expanding with
development, thereby increasing the search area of larvae. Pre-strike distances of early larvae were substantially less than
one body length, being constantly around a 1/3 of a body length for all larval ages examined. 相似文献
917.
Nohrdent D Cattaneo C Gabriel P Ohlrogge S Poppa P Schmitt R Tutkuviene J Rizgeliene R Ratnayake M Obertová Z Ritz-Timme S 《Anthropologischer Anzeiger; Bericht über die biologisch-anthropologische Literatur》2010,68(1):101-109
Recruiting test persons is crucial in many scientific fields. The recognition of motivators or barriers to survey participation may support the design and recruitment strategy of future studies. The recruitment of under age test persons is very complex and sensitive. This paperpresents and analyses the experiences in recruitment of female juveniles (10-18 years old) in Germany, Italy and Lithuania within the context of an EU funded project concerning the extremely sensitive topic of "child pornography". The purpose of the project was to develop a method for age estimation of juveniles on photographs and videos. The faces of the test persons were photographed and anthropologically measured after an informed consent was signed by their parents and themselves. The analysis of the recruitment strategies and response rates revealed that culturally influenced factors played a significant role in the individual decision for or against a participation in the study. In all countries, the sensitive topic of child pornography had a great influence on the decision process. Many German parents agreed especially in light of this topic while in Italy and Lithuania the word "child pornography" triggered a very negative response. In Germany, the anthropological investigation of the faces provoked negative associations with the anthropometric surveys in the Third Reich. Social and political climate were further relevant factors for decision-making especially in Lithuania. The "top-down" principle of recruitment proved to be very effective for this kind of study. The authorities of headmasters, scientists and institutions positively influenced the decisions of the parents. 相似文献
918.
Melanie Schwarten Matthias Stoldt Jeannine Mohrlüder 《Biochemical and biophysical research communications》2010,395(3):426-973
During autophagy a crescent shaped like membrane is formed, which engulfs the material that is to be degraded. This membrane grows further until its edges fuse to form the double membrane covered autophagosome. Atg8 is a protein, which is required for this initial step of autophagy. Therefore, a multistage conjugation process of newly synthesized Atg8 to phosphatidylethanolamine is of critical importance. Here we present the high resolution structure of unprocessed Atg8 determined by nuclear magnetic resonance spectroscopy. Its C-terminal subdomain shows a well-defined ubiquitin-like fold with slightly elevated mobility in the pico- to nanosecond timescale as determined by heteronuclear NOE data. In comparison to unprocessed Atg8, cleaved Atg8G116 shows a decreased mobility behaviour. The N-terminal domain adopts different conformations within the micro- to millisecond timescale. The possible biological relevance of the differences in dynamic behaviours between both subdomains as well as between the cleaved and uncleaved forms is discussed. 相似文献
919.
Heney M Alipour M Vergidis D Omri A Mugabe C Th'ng J Suntres Z 《Canadian journal of physiology and pharmacology》2010,88(12):1172-1180
Paclitaxel is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including breast, ovarian, and non-small-cell lung cancer. Due to its high lipophilicity, paclitaxel is difficult to administer and requires solubilization with Cremophor EL (polyethoxylated castor oil) and ethanol, which often lead to adverse side effects, including life-threatening anaphylaxis. Incorporation of paclitaxel in dimyristoylphosphatidylcholine:dimyristoylphosphatidylglycerol (DPPC:DMPG) liposomes can facilitate its delivery to cancer cells and eliminate the adverse reactions associated with the Cremophor EL vehicle. Accordingly, the effectiveness of liposomal paclitaxel on MCF-7 breast cancer cells was examined. The results from this study showed that (i) the lipid components of the liposomal formulation were nontoxic, (ii) the cytotoxic effects of liposomal paclitaxel were improved when compared with those seen with conventional paclitaxel, and (iii) the intracellular paclitaxel levels were higher in MCF-7 cells treated with the liposomal paclitaxel formulation. The results of these studies showed that delivery of paclitaxel as a liposomal formulation could be a promising strategy for enhancing its chemotherapeutic effects. 相似文献
920.