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排序方式: 共有684条查询结果,搜索用时 187 毫秒
101.
Saima M. Sidik Miryam A. Hortua Triana Aditya S. Paul Majida El Bakkouri Caroline G. Hackett Fanny Tran Nicholas J. Westwood Raymond Hui William J. Zuercher Manoj T. Duraisingh Silvia N. J. Moreno Sebastian Lourido 《The Journal of biological chemistry》2016,291(18):9566-9580
The life cycles of apicomplexan parasites progress in accordance with fluxes in cytosolic Ca2+. Such fluxes are necessary for events like motility and egress from host cells. We used genetically encoded Ca2+ indicators (GCaMPs) to develop a cell-based phenotypic screen for compounds that modulate Ca2+ signaling in the model apicomplexan Toxoplasma gondii. In doing so, we took advantage of the phosphodiesterase inhibitor zaprinast, which we show acts in part through cGMP-dependent protein kinase (protein kinase G; PKG) to raise levels of cytosolic Ca2+. We define the pool of Ca2+ regulated by PKG to be a neutral store distinct from the endoplasmic reticulum. Screening a library of 823 ATP mimetics, we identify both inhibitors and enhancers of Ca2+ signaling. Two such compounds constitute novel PKG inhibitors and prevent zaprinast from increasing cytosolic Ca2+. The enhancers identified are capable of releasing intracellular Ca2+ stores independently of zaprinast or PKG. One of these enhancers blocks parasite egress and invasion and shows strong antiparasitic activity against T. gondii. The same compound inhibits invasion of the most lethal malaria parasite, Plasmodium falciparum. Inhibition of Ca2+-related phenotypes in these two apicomplexan parasites suggests that depletion of intracellular Ca2+ stores by the enhancer may be an effective antiparasitic strategy. These results establish a powerful new strategy for identifying compounds that modulate the essential parasite signaling pathways regulated by Ca2+, underscoring the importance of these pathways and the therapeutic potential of their inhibition. 相似文献
102.
Markus V. Heppt Thomas K. Eigentler Katharina C. Kähler Rudolf A. Herbst Daniela Göppner Thilo Gambichler Jens Ulrich Edgar Dippel Carmen Loquai Beatrice Schell Bastian Schilling Susanne G. Schäd Erwin S. Schultz Fanny Matheis Julia K. Tietze Carola Berking 《Cancer immunology, immunotherapy : CII》2016,65(8):951-959
103.
Solution structures and model membrane interactions of lactoferrampin, an antimicrobial peptide derived from bovine lactoferrin 总被引:2,自引:0,他引:2
Bovine lactoferrampin (LFampinB) has been identified as a novel antimicrobial peptide, which is derived from the N-terminal lobe of bovine lactoferrin. In this study, the solution structure of LFampinB bound to negatively charged sodium dodecyl sulphate micelles and zwitterionic dodecyl phosphocholine micelles was determined using 2-dimensional nuclear magnetic resonance (NMR) spectroscopy. The interaction between LFampinB and multilamellar phospholipid vesicles, containing choline and glycerol head groups, was examined using differential scanning calorimetry (DSC). In addition, the interaction between the N-terminal tryptophan residue and model membranes of varying composition was analyzed by fluorescence spectroscopy. LFampinB adopts an amphipathic alpha-helical conformation across the first 11 residues of the peptide but remains relatively unstructured at the C-terminus. The hydrophobic surface of the amphipathic helix is bordered by the side chains of Trp1 and Phe11, and is seen in both micelle-bound structures. The fluorescence results suggest that Trp1 inserts into the membrane at the lipid/water interface. The phenyl side chain of Phe11 is oriented in the same direction as the indole ring of Trp1, allowing these two residues to serve as anchors for the lipid bilayer. The DSC results also indicate that LFampinB interacts with glycerol head groups in multilamellar vesicles but has little effect on acyl chain packing. Our results support a two step model of antimicrobial activity where the initial attraction of LFampinB is mediated by the cluster of positive charges on the C-terminus followed by the formation of the N-terminal helix which binds to the surface of the bacterial lipid bilayer. 相似文献
104.
105.
Clinico‐molecular analysis of eleven patients with Hermansky–Pudlak type 5 syndrome,a mild form of HPS
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Vincent Michaud Eulalie Lasseaux Claudio Plaisant Alain Verloes Yaumara Perdomo‐Trujillo Christian Hamel Nursel H. Elcioglu Bart Leroy Josseline Kaplan Pierre‐Simon Jouk Didier Lacombe Patricia Fergelot Fanny Morice‐Picard Benoit Arveiler 《Pigment cell & melanoma research》2017,30(6):563-570
Hermansky–Pudlak syndrome (HPS), first described in 1959, is a rare form of syndromic oculocutaneous albinism associated with bleeding diathesis and in some cases pulmonary fibrosis and granulomatous colitis. All 10 HPS types are caused by defects in vesicle trafficking of lysosome‐related organelles (LRO) proteins. The HPS5 protein associates with HPS3 and HPS6 to form the biogenesis of lysosome‐related organelles complex‐2 (BLOC‐2). Here, we report the clinical and genetic data of 11 patients with HPS‐5 analyzed in our laboratory. We report 11 new pathogenic variants. The 11 patients present with ocular features that are typical for albinism, with mild hypopigmentation, and with no other major complication, apart from a tendency to bleed. HPS‐5 therefore appears as a mild form of HPS, which is often clinically undistinguishable from mild oculocutaneous or ocular forms of albinism. Molecular analysis is therefore required to establish the diagnosis of this mild HPS form, which has consequences in terms of prognosis and of clinical management of the patients. 相似文献
106.
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108.
Nathalie Sibille Xavier Hanoulle Fanny Bonachera Dries Verdegem Isabelle Landrieu Jean-Michel Wieruszeski Guy Lippens 《Journal of biomolecular NMR》2009,43(4):219-227
Adding the 13C labelled 2-keto-isovalerate and 2-oxobutanoate precursors to a minimal medium composed of 12C labelled glucose instead of the commonly used (2D, 13C) glucose leads not only to the 13C labelling of (I, L, V) methyls but also to the selective 13C labelling of the backbone Cα and CO carbons of the Ile and Val residues. As a result, the backbone (1H, 15N) correlations of the Ile and Val residues and their next neighbours in the (i + 1) position can be selectively identified in HN(CA) and HN(CO) planes. The availability of a selective HSQC spectrum corresponding
to the sole amide resonances of the Ile and Val residues allows connecting them to their corresponding methyls by the intra-residue
NOE effect, and should therefore be applicable to larger systems. 相似文献
109.
Gregor Kozlowski Sandra Bürcher Matthieu Fleury Fanny Huber 《Biodiversity and Conservation》2009,18(3):649-662
The purpose of this study was to examine the composition, distribution, ecology, and conservation status of the Atlantic elements
of the Swiss flora. About 195 Atlantic and 80 Mediterranean–Atlantic vascular plant species of the European flora have been
used as the basis for our analysis. The complete list of 3,143 taxa has been used as the reference for the Swiss flora. The
distributions of the species are illustrated in coincidence maps based on the computer database of the Data Centre of the
Swiss Flora in Geneva, Switzerland. Our study demonstrates clearly that the Atlantic flora of Europe requires a new biogeographical
appraisal. The Swiss flora comprises 66 Atlantic and Mediterranean–Atlantic taxa, which are taxonomically and ecologically
highly diverse. Switzerland contains 44% of all European Sub-Atlantic plants. This confirms the Sub-Atlantic geographical
position of Switzerland. Only one Eu-Atlantic species growing in Switzerland, Vicia orobus, can be classified as native with certainty. This species is critically endangered and merits the highest conservation priority.
Although a very alpine country, Switzerland has a relatively large number of Mediterranean–Atlantic species. The Atlantic
and Mediterranean–Atlantic plants are a very threatened group in Switzerland, with wetland plants the most imperilled ecological
group.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
110.
Jochen Heinrichs Fanny Klugmann Jrn Hentschel Harald Schneider 《Molecular phylogenetics and evolution》2009,53(1):113-121
The Neotropical-African liverwort Marchesinia brachiata has long been regarded as a polymorphic species. This hypothesis is examined using a dataset including sequences of the nuclear internal transcribed spacer region and the plastidic trnL–trnF region of 39 Marchesinia accessions. Maximum parsimony, maximum likelihood and Bayesian analyses indicate that Marchesinia robusta is nested within M. brachiata s.l. The molecular topologies support at least three partly sympatric biological species within M. brachiata s.l., the Neotropical M. bongardiana and M. languida, and the Neotropical-African M. brachiata s.s. These species are incompletely separated by subtle differences in underleaf shape and leaf dentation. Long branches within M. brachiata s.s. suggest ongoing speciation processes that are not yet reflected in distinguishable morphological variation. Divergence time estimates based on nrITS sequence variation and the liverwort fossil record indicate an establishment of the species M. bongardiana, M. brachiata, M. languida, M. madagassa, and M. robusta in the Late Oligocene and Miocene. The intraspecific diversity shows distinctive patterns with evidence for constant accumulation of genetic diversity in M. robusta and M. brachiata whereas M. bongardiana and M. languida likely went through a recent extinction or expansion process as indicated by the bottleneck pattern of genetic diversity. The tropical American-African disjunction of M. brachiata is the result of dispersal rather than Western Gondwanan vicariance. 相似文献