全文获取类型
收费全文 | 643篇 |
免费 | 73篇 |
出版年
2022年 | 8篇 |
2021年 | 9篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2017年 | 6篇 |
2016年 | 19篇 |
2015年 | 33篇 |
2014年 | 39篇 |
2013年 | 42篇 |
2012年 | 43篇 |
2011年 | 43篇 |
2010年 | 24篇 |
2009年 | 19篇 |
2008年 | 29篇 |
2007年 | 23篇 |
2006年 | 33篇 |
2005年 | 28篇 |
2004年 | 29篇 |
2003年 | 22篇 |
2002年 | 27篇 |
2001年 | 19篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 3篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1981年 | 3篇 |
1980年 | 8篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1971年 | 5篇 |
1969年 | 3篇 |
1966年 | 3篇 |
1961年 | 3篇 |
1957年 | 3篇 |
1912年 | 3篇 |
排序方式: 共有716条查询结果,搜索用时 265 毫秒
111.
Kaiser C Dobrikova EY Bradrick SS Shveygert M Herbert JT Gromeier M 《RNA (New York, N.Y.)》2008,14(10):2170-2182
Protein synthesis is tightly controlled by assembly of an intricate ribonucleoprotein complex at the m7GTP-cap on eukaryotic mRNAs. Ensuing linear scanning of the 5′ untranslated region (UTR) is believed to transfer the preinitiation complex to the initiation codon. Eukaryotic mRNAs are characterized by significant 5′ UTR heterogeneity, raising the possibility of differential control of translation initiation rate at individual mRNAs. Curiously, many mRNAs with unconventional, highly structured 5′ UTRs encode proteins with central biological roles in growth control, metabolism, or stress response. The 5′ UTRs of such mRNAs may influence protein synthesis rate in multiple ways, but most significantly they have been implicated in mediating alternative means of translation initiation. Cap-independent initiation bypasses strict control over the formation of initiation intermediates at the m7GTP cap. However, the molecular mechanisms that favor alternative means of ribosome recruitment are not understood. Here we provide evidence that eukaryotic initiation factor (eIF) 4G controls cap-independent translation initiation at the c-myc and vascular endothelial growth factor (VEGF) 5′ UTRs in vivo. Cap-independent translation was investigated in tetracycline-inducible cell lines expressing either full-length eIF4G or a C-terminal fragment (Ct) lacking interaction with eIF4E and poly(A) binding protein. Expression of Ct, but not intact eIF4G, potently stimulated cap-independent initiation at the c-myc/VEGF 5′ UTRs. In vitro RNA-binding assays suggest that stimulation of cap-independent translation initiation by Ct is due to direct association with the c-myc/VEGF 5′ UTR, enabling 43S preinitiation complex recruitment. Our work demonstrates that variant translation initiation factors enable unconventional translation initiation at mRNA subsets with distinct structural features. 相似文献
112.
Böttcher C von Roepenack-Lahaye E Schmidt J Schmotz C Neumann S Scheel D Clemens S 《Plant physiology》2008,147(4):2107-2120
Metabolomics is facing a major challenge: the lack of knowledge about metabolites present in a given biological system. Thus, large-scale discovery of metabolites is considered an essential step toward a better understanding of plant metabolism. We show here that the application of a metabolomics approach generating structural information for the analysis of Arabidopsis (Arabidopsis thaliana) mutants allows the efficient cataloging of metabolites. Fifty-six percent of the features that showed significant differences in abundance between seeds of wild-type, transparent testa4, and transparent testa5 plants could be annotated. Seventy-five compounds were structurally characterized, 21 of which could be identified. About 40 compounds had not been known from Arabidopsis before. Also, the high-resolution analysis revealed an unanticipated expansion of metabolic conversions upstream of biosynthetic blocks. Deficiency in chalcone synthase results in the increased seed-specific biosynthesis of a range of phenolic choline esters. Similarly, a lack of chalcone isomerase activity leads to the accumulation of various naringenin chalcone derivatives. Furthermore, our data provide insight into the connection between p-coumaroyl-coenzyme A-dependent pathways. Lack of flavonoid biosynthesis results in elevated synthesis not only of p-coumarate-derived choline esters but also of sinapate-derived metabolites. However, sinapoylcholine is not the only accumulating end product. Instead, we observed specific and sophisticated changes in the complex pattern of sinapate derivatives. 相似文献
113.
Bernd Heimrich Daniel-Alexander Hesse Yuan-Ju Wu Sonja Schmid Martin Schwemmle 《Cell and tissue research》2009,338(2):179-190
Granule cells are major targets of entorhinal afferents terminating in a laminar fashion in the outer molecular layer of the
dentate gyrus. Since Borna disease virus (BDV) infection of newborn rats causes a progressive loss of granule cells in the
dentate gyrus, entorhinal fibres become disjoined from their main targets. We have investigated the extent to which entorhinal
axons react to this loss of granule cells. Unexpectedly, anterograde DiI tracing has shown a prominent layered termination
of the entorhinal projection, despite an almost complete loss of granule cells at 9 weeks after infection. Combined light-
and electron-microscopic analysis of dendrites at the outer molecular layer of the dentate gyrus at 6 and 9 weeks post-infection
has revealed a transient increase in the synaptic density of calbindin-positive granule cells and parvalbuminergic neurons
after 6 weeks. In contrast, synaptic density reaches values similar to those of uninfected controls 9 weeks post-infection.
These findings indicate that, after BDV infection, synaptic reorganization processes occur at peripheral dendrites of the
remaining granule cells and parvalbuminergic neurons, including the unexpected persistence of entorhinal axons in the absence
of their main targets. 相似文献
114.
115.
Dmitri Demidov Susann Hesse Annegret Tewes Twan Rutten Jörg Fuchs Raheleh Karimi Ashtiyani Sandro Lein reas Fischer Gunter Reuter Andreas Houben 《The Plant journal : for cell and molecular biology》2009,59(2):221-230
The enzymological properties of AtAurora1, a kinase responsible for the cell cycle-dependent phosphorylation of histone H3 at S10, and its cross-talk with other post-translational histone modifications, were determined. In vitro phosphorylation of H3S10 by AtAurora1 is strongly increased by K9 acetylation, and decreased by K14 acetylation and T11 phosphorylation. However, S10 phosphorylation activity is unaltered by mono-, di- or trimethylation of K9. An interference of H3K9 dimethylation by SUVR4 occurs by a pre-existing phosphorylation at S10. Hence, cross-talk in plants exists between phosphorylation of H3S10 and methylation, acetylation or phosphorylation of neighbouring amino acid residues. AtAurora1 undergoes autophosphorylation in vivo regardless of the presence of substrate, and forms dimers in planta . Of the three ATP-competitive Aurora inhibitors tested, Hesperadin was most effective in reducing the in vivo kinase activity of AtAurora1. Hesperadin consistently inhibited histone H3S10 phosphorylation during mitosis in Arabidopsis cells, but did not affect other H3 post-translational modifications, suggesting a specific inhibition of AtAurora in vivo . Inactivation of AtAurora also caused lagging chromosomes in a number of anaphase cells, but, unlike the situation in mammalian cells, Hesperadin did not influence the microtubule dynamics in dividing cells. 相似文献
116.
Soledad Galli Olaf Jahn Reiner Hitt Doerte Hesse Lennart Opitz Uwe Plessmann Henning Urlaub Juan Jose Poderoso Elizabeth A. Jares-Erijman Thomas M. Jovin 《PloS one》2009,4(10)
Extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) are members of the MAPK family and participate in the transduction of stimuli in cellular responses. Their long-term actions are accomplished by promoting the expression of specific genes whereas faster responses are achieved by direct phosphorylation of downstream effectors located throughout the cell. In this study we determined that hERK1 translocates to the mitochondria of HeLa cells upon a proliferative stimulus. In the mitochondrial environment, hERK1 physically associates with (i) at least 5 mitochondrial proteins with functions related to transport (i.e. VDAC1), signalling, and metabolism; (ii) histones H2A and H4; and (iii) other cytosolic proteins. This work indicates for the first time the presence of diverse ERK-complexes in mitochondria and thus provides a new perspective for assessing the functions of ERK1 in the regulation of cellular signalling and trafficking in HeLa cells. 相似文献
117.
Correction: Caldendrin–Jacob: A Protein Liaison That Couples NMDA Receptor Signalling to the Nucleus
Daniela C Dieterich Anna Karpova Marina Mikhaylova Irina Zdobnova Imbritt K?nig Marco Landwehr Martin Kreutz Karl-Heinz Smalla Karin Richter Peter Landgraf Carsten Reissner Tobias M Boeckers Werner Zuschratter Christina Spilker Constanze I Seidenbecher Craig C Garner Eckart D Gundelfinger Michael R Kreutz 《PLoS biology》2009,7(1)
118.
Andreas Wilting Anna Cord Andrew J. Hearn Deike Hesse Azlan Mohamed Carl Traeholdt Susan M. Cheyne Sunarto Sunarto Mohd-Azlan Jayasilan Joanna Ross Aurélie C. Shapiro Anthony Sebastian Stefan Dech Christine Breitenmoser Jim Sanderson J. W. Duckworth Heribert Hofer 《PloS one》2010,5(3)
Background
The flat-headed cat (Prionailurus planiceps) is one of the world''s least known, highly threatened felids with a distribution restricted to tropical lowland rainforests in Peninsular Thailand/Malaysia, Borneo and Sumatra. Throughout its geographic range large-scale anthropogenic transformation processes, including the pollution of fresh-water river systems and landscape fragmentation, raise concerns regarding its conservation status. Despite an increasing number of camera-trapping field surveys for carnivores in South-East Asia during the past two decades, few of these studies recorded the flat-headed cat.Methodology/Principal Findings
In this study, we designed a predictive species distribution model using the Maximum Entropy (MaxEnt) algorithm to reassess the potential current distribution and conservation status of the flat-headed cat. Eighty-eight independent species occurrence records were gathered from field surveys, literature records, and museum collections. These current and historical records were analysed in relation to bioclimatic variables (WorldClim), altitude (SRTM) and minimum distance to larger water resources (Digital Chart of the World). Distance to water was identified as the key predictor for the occurrence of flat-headed cats (>50% explanation). In addition, we used different land cover maps (GLC2000, GlobCover and SarVision LLC for Borneo), information on protected areas and regional human population density data to extract suitable habitats from the potential distribution predicted by the MaxEnt model. Between 54% and 68% of suitable habitat has already been converted to unsuitable land cover types (e.g. croplands, plantations), and only between 10% and 20% of suitable land cover is categorised as fully protected according to the IUCN criteria. The remaining habitats are highly fragmented and only a few larger forest patches remain.Conclusion/Significance
Based on our findings, we recommend that future conservation efforts for the flat-headed cat should focus on the identified remaining key localities and be implemented through a continuous dialogue between local stakeholders, conservationists and scientists to ensure its long-term survival. The flat-headed cat can serve as a flagship species for the protection of several other endangered species associated with the threatened tropical lowland forests and surface fresh-water sources in this region. 相似文献119.
Steinacker P Awni LA Becker S Cole T Reymann S Hesse D Kratzin HD Morris-Wortmann C Schwarzer C Thinnes FP Hilschmann N 《The international journal of biochemistry & cell biology》2000,32(2):225-234
Recent patch-clamp studies have shown that anti-porin antibodies, applied to the external side of excised plasma membrane patches of mammalian astrocytes, close chloride channels that are thought to be engaged in cell volume regulation. Frog oocytes are often used to study this basic cell function. Here we document the localisation of endogenous porin voltage-dependent anion-selective channels in Xenopus laevis oocyte plasma membranes. In confocal laser microscopy images a disjunctive pattern of fluorescing spots appear about 10 microm apart. Labelling was prevented by preabsorption of the antibodies with synthetic peptides comprising the epitope of the antigen. Immuno-gold marking of oocyte surfaces followed by silver enhancement of the gold particles lead to a plasma membrane labelling corresponding to that obtained by the confocal laser approach. The data suggests the presence of voltage-dependent, anion-selective channels in oocyte plasma membranes. This data should be borne in mind when frog oocytes are used to study the characteristics of endogenous or heterologously expressed ion channels or regulatory proteins. 相似文献
120.
Stuiver M Lainez S Will C Terryn S Günzel D Debaix H Sommer K Kopplin K Thumfart J Kampik NB Querfeld U Willnow TE Němec V Wagner CA Hoenderop JG Devuyst O Knoers NV Bindels RJ Meij IC Müller D 《American journal of human genetics》2011,88(3):333-343
Familial hypomagnesemia is a rare human disorder caused by renal or intestinal magnesium (Mg(2+)) wasting, which may lead to symptoms of Mg(2+) depletion such as tetany, seizures, and cardiac arrhythmias. Our knowledge of the physiology of Mg(2+) (re)absorption, particularly the luminal uptake of Mg(2+) along the nephron, has benefitted from positional cloning approaches in families with Mg(2+) reabsorption disorders; however, basolateral Mg(2+) transport and its regulation are still poorly understood. Here, by using a candidate screening approach, we identified CNNM2 as a gene involved in renal Mg(2+) handling in patients of two unrelated families with unexplained dominant hypomagnesemia. In the kidney, CNNM2 was predominantly found along the basolateral membrane of distal tubular segments involved in Mg(2+) reabsorption. The basolateral localization of endogenous and recombinant CNNM2 was confirmed in epithelial kidney cell lines. Electrophysiological analysis showed that CNNM2 mediated Mg(2+)-sensitive Na(+) currents that were significantly diminished in mutant protein and were blocked by increased extracellular Mg(2+) concentrations. Our data support the findings of a recent genome-wide association study showing the CNNM2 locus to be associated with serum Mg(2+) concentrations. The mutations found in CNNM2, its observed sensitivity to extracellular Mg(2+), and its basolateral localization signify a critical role for CNNM2 in epithelial Mg(2+) transport. 相似文献