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81.
82.
Kerstin Radtke Daniela Kieneke André Wolfstein Kathrin Michael Walter Steffen Tim Scholz Axel Karger Beate Sodeik 《PLoS pathogens》2010,6(7)
Many viruses depend on host microtubule motors to reach their destined intracellular location. Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 (HSV1) show bidirectional transport towards the cell center as well as the periphery, indicating that they utilize microtubule motors of opposing directionality. To understand the mechanisms of specific motor recruitment, it is necessary to characterize the molecular composition of such motile viral structures. We have generated HSV1 capsids with different surface features without impairing their overall architecture, and show that in a mammalian cell-free system the microtubule motors dynein and kinesin-1 and the dynein cofactor dynactin could interact directly with capsids independent of other host factors. The capsid composition and surface was analyzed with respect to 23 structural proteins that are potentially exposed to the cytosol during virus assembly or cell entry. Many of these proteins belong to the tegument, the hallmark of all herpesviruses located between the capsid and the viral envelope. Using immunoblots, quantitative mass spectrometry and quantitative immunoelectron microscopy, we show that capsids exposing inner tegument proteins such as pUS3, pUL36, pUL37, ICP0, pUL14, pUL16, and pUL21 recruited dynein, dynactin, kinesin-1 and kinesin-2. In contrast, neither untegumented capsids exposing VP5, VP26, pUL17 and pUL25 nor capsids covered by outer tegument proteins such as vhs, pUL11, ICP4, ICP34.5, VP11/12, VP13/14, VP16, VP22 or pUS11 bound microtubule motors. Our data suggest that HSV1 uses different structural features of the inner tegument to recruit dynein or kinesin-1. Individual capsids simultaneously accommodated motors of opposing directionality as well as several copies of the same motor. Thus, these associated motors either engage in a tug-of-war or their activities are coordinately regulated to achieve net transport either to the nucleus during cell entry or to cytoplasmic membranes for envelopment during assembly. 相似文献
83.
Kathrin Rychli Christoph Kaun Philipp J. Hohensinner Adrian J. Dorfner Stefan Pfaffenberger Alexander Niessner Michael Bauer Wolfgang Dietl Bruno K. Podesser Gerald Maurer Kurt Huber Johann Wojta 《Journal of cellular and molecular medicine》2010,14(1-2):198-205
Cardiac diseases such as myocardial infarction and heart failure are among the leading causes of death in western societies. Therapeutic angiogenesis has been suggested as a concept to combat these diseases. The biology of angiogenic factors expressed in the heart such as vascular endothelial growth factor (VEGF) is well studied, whereas data on anti-angiogenic mediators in the heart are scarce. Here we study the expression of the anti-angiogenic factor pigment epithelium-derived factor (PEDF) in the human heart and in human cardiac cells. PEDF expression could be detected in human cardiac tissue on the protein and mRNA levels. PEDF mRNA levels were significantly lower in explanted human ischemic hearts as compared to healthy hearts. Our in vitro experiments showed that human adult cardiac myocytes and fibroblasts constitutively secrete PEDF. In addition to anoxic conditions, cobalt chloride, 2,2'dipyridyl and dimethoxally glycine, which stabilize hypoxia inducible factor-α decreased PEDF expression. Furthermore we show that PEDF inhibits VEGF-induced sprouting. We have identified PEDF in healthy and ischemic human hearts and we show that PEDF expression is down-regulated by low oxygen levels. Therefore, we suggest a role for PEDF in the regulation of angiogenesis in the heart and propose PEDF as a possible therapeutic target in heart disease. 相似文献
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86.
Mauricio Hunsche Kathrin Bürling Amina Sirag Saied Michaela Schmitz-Eiberger Muhammad Sohail Jens Gebauer Georg Noga Andreas Buerkert 《Plant Growth Regulation》2010,61(3):253-263
Seedlings of the salt-tolerant plant grewia [Grewia tenax (Forssk.) Fiori] and the moderately salt-tolerant tamarind (Tamarindus indica L.) were grown under controlled conditions and treated daily with NaCl solutions to investigate mechanisms of tolerance to
salinity. Leaf micromorphology, cuticular wax load, chlorophyll fluorescence and light remission, as well as antioxidative
potential were evaluated. As confirmed by energy-dispersive X-ray microanalysis in both species, absorption of sodium and
chlorine increased with rising NaCl concentration in the treatment solution. In parallel, accumulation of calcium in grewia
leaves was strongly reduced, leading to less crystals of calcium oxalate in leaf tissue. In grewia the cuticular wax load,
chlorophyll content, and electron transport rate (ETR) were significantly reduced by comparatively low NaCl concentrations.
In tamarind, in contrast, wax load and ETR were not significantly affected, while the decrease of chlorophyll content was
less pronounced. Measurements of the antioxidative capacity and the imbalance between values of lipophilic and hydrophilic
extracts at different NaCl concentrations confirmed that grewia is more salt tolerant than tamarind. This higher tolerance
degree seemed to be associated with grewias’ more efficient scavenging of free radicals and the regulation of the antioxidative
potential in lipophilic and hydrophilic extracts. 相似文献
87.
Li Y Laue K Temtamy S Aglan M Kotan LD Yigit G Canan H Pawlik B Nürnberg G Wakeling EL Quarrell OW Baessmann I Lanktree MB Yilmaz M Hegele RA Amr K May KW Nürnberg P Topaloglu AK Hammerschmidt M Wollnik B 《American journal of human genetics》2010,87(6):757-767
Altered Bone Morphogenetic Protein (BMP) signaling leads to multiple developmental defects, including brachydactyly and deafness. Here we identify chondroitin synthase 1 (CHSY1) as a potential mediator of BMP effects. We show that loss of human CHSY1 function causes autosomal-recessive Temtamy preaxial brachydactyly syndrome (TPBS), mainly characterized by limb malformations, short stature, and hearing loss. After mapping the TPBS locus to chromosome 15q26-qterm, we identified causative mutations in five consanguineous TPBS families. In zebrafish, antisense-mediated chsy1 knockdown causes defects in multiple developmental processes, some of which are likely to also be causative in the etiology of TPBS. In the inner ears of zebrafish larvae, chsy1 is expressed similarly to the BMP inhibitor dan and in a complementary fashion to bmp2b. Furthermore, unrestricted Bmp2b signaling or loss of Dan activity leads to reduced chsy1 expression and, during epithelial morphogenesis, defects similar to those that occur upon Chsy1 inactivation, indicating that Bmp signaling affects inner-ear development by repressing chsy1. In addition, we obtained strikingly similar zebrafish phenotypes after chsy1 overexpression, which might explain why, in humans, brachydactyly can be caused by mutations leading either to loss or to gain of BMP signaling. 相似文献
88.
Sandra Andorf Joachim Selbig Thomas Altmann Kathrin Poos Hanna Witucka-Wall Dirk Repsilber 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(2):249-259
Heterosis is a well-known phenomenon but the underlying molecular mechanisms are not yet established. To contribute to the
understanding of heterosis at the molecular level, we analyzed genome-wide gene expression profile data of Arabidopsis thaliana in a systems biological approach. We used partial correlations to estimate the global interaction structure of regulatory
networks. Our hypothesis states that heterosis comes with an increased number of partial correlations which we interpret as
increased numbers of regulatory interactions leading to enlarged adaptability of the hybrids. This hypothesis is true for
mid-parent heterosis for our dataset of gene expression in two homozygous parental lines and their reciprocal crosses. For
the case of best-parent heterosis just one hybrid is significant regarding our hypothesis based on a resampling analysis.
Summarizing, both metabolome and gene expression level of our illustrative dataset support our proposal of a systems biological
approach towards a molecular basis of heterosis. 相似文献
89.
90.
Gra?yna Domańska Christian Motz Michael Meinecke Anke Harsman Panagiotis Papatheodorou Boris Reljic Elke A. Dian-Lothrop Antoine Galmiche Oliver Kepp Lars Becker Kathrin Günnewig Richard Wagner Joachim Rassow 《PLoS pathogens》2010,6(4)
The vacuolating toxin VacA, released by Helicobacter pylori, is an important virulence factor in the pathogenesis of gastritis and gastroduodenal ulcers. VacA contains two subunits: The p58 subunit mediates entry into target cells, and the p34 subunit mediates targeting to mitochondria and is essential for toxicity. In this study we found that targeting to mitochondria is dependent on a unique signal sequence of 32 uncharged amino acid residues at the p34 N-terminus. Mitochondrial import of p34 is mediated by the import receptor Tom20 and the import channel of the outer membrane TOM complex, leading to insertion of p34 into the mitochondrial inner membrane. p34 assembles in homo-hexamers of extraordinary high stability. CD spectra of the purified protein indicate a content of >40% β-strands, similar to pore-forming β-barrel proteins. p34 forms an anion channel with a conductivity of about 12 pS in 1.5 M KCl buffer. Oligomerization and channel formation are independent both of the 32 uncharged N-terminal residues and of the p58 subunit of the toxin. The conductivity is efficiently blocked by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), a reagent known to inhibit VacA-mediated apoptosis. We conclude that p34 essentially acts as a small pore-forming toxin, targeted to the mitochondrial inner membrane by a special hydrophobic N-terminal signal. 相似文献