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681.
Maximilian Kühnle Diana Kreidler Karsten Holtin Harri Czesla Paul Schuler Volker Schurig Klaus Albert 《Chirality》2010,22(9):808-812
The hyphenation of enantioselective capillary gas chromatography and mass spectrometry is not always sufficient to distinguish between structural isomers, thus requiring peak identification by NMR spectroscopy. Here the first online coupling of enantioselective capillary gas chromatography with proton nuclear resonance spectroscopy is described for the unfunctionalized chiral alkane 2,4‐dimethylhexane resolved on octakis(6‐O‐methyl‐2,3‐di‐O‐pentyl)‐γ‐cyclodextrin at 60°C. NMR allows constitutional and configurational isomers (diastereomers and enantiomers) to be distinguished. Enantiomers display identical spectra at different retention times, which enable an indirect identification of these unfunctionalized alkanes. The presented method is still at an early development stage, and will require instrumental optimization in the future. Chirality 2010. © 2010 Wiley‐Liss, Inc. 相似文献
682.
Erich Roessler Yong Ma Maia V. Ouspenskaia Felicitas Lacbawan Claude Bendavid Christèle Dubourg Philip A. Beachy Maximilian Muenke 《Human genetics》2009,125(4):393-400
Defective function of the Sonic Hedgehog (SHH) signaling pathway is the most frequent alteration underlying holoprosencephaly
(HPE) or its various clinical microforms. We performed an extensive mutational analysis of the entire human DISP1 gene, required for secretion of all hedgehog ligand(s) and which maps to the HPE 10 locus of human chromosome 1q41, as a
HPE candidate gene. Here, we describe two independent families with truncating mutations in human DISP1 that resemble the cardinal craniofacial and neuro-developmental features of a recently described microdeletion syndrome that
includes this gene; therefore, we suggest that DISP1 function contributes substantially to both of these signs in humans. While these clinical features are consistent with common
HPE microforms, especially those linked to defective signaling by Sonic Hedgehog, we have insufficient evidence so far that
functionally abnormal DISP1 alleles will commonly contribute to the more severe features of typical HPE. 相似文献
683.
684.
685.
Janine Hochmair Christian Exner Maximilian Franck Alvaro DominguezBaquero Lisa Diez Hvila Brognaro Matthew L Kraushar Thorsten Mielke Helena Radbruch Senthilvelrajan Kaniyappan Sven Falke Eckhard Mandelkow Christian Betzel Susanne Wegmann 《The EMBO journal》2022,41(11)
Biomolecular condensation of the neuronal microtubule‐associated protein Tau (MAPT) can be induced by coacervation with polyanions like RNA, or by molecular crowding. Tau condensates have been linked to both functional microtubule binding and pathological aggregation in neurodegenerative diseases. We find that molecular crowding and coacervation with RNA, two conditions likely coexisting in the cytosol, synergize to enable Tau condensation at physiological buffer conditions and to produce condensates with a strong affinity to charged surfaces. During condensate‐mediated microtubule polymerization, their synergy enhances bundling and spatial arrangement of microtubules. We further show that different Tau condensates efficiently induce pathological Tau aggregates in cells, including accumulations at the nuclear envelope that correlate with nucleocytoplasmic transport deficits. Fluorescent lifetime imaging reveals different molecular packing densities of Tau in cellular accumulations and a condensate‐like density for nuclear‐envelope Tau. These findings suggest that a complex interplay between interaction partners, post‐translational modifications, and molecular crowding regulates the formation and function of Tau condensates. Conditions leading to prolonged existence of Tau condensates may induce the formation of seeding‐competent Tau and lead to distinct cellular Tau accumulations. 相似文献
686.
Andrew A. Bridges Maximilian S. Jentzsch Patrick W. Oakes Patricia Occhipinti Amy S. Gladfelter 《The Journal of cell biology》2016,213(1):23-32
Cells change shape in response to diverse environmental and developmental conditions, creating topologies with micron-scale features. Although individual proteins can sense nanometer-scale membrane curvature, it is unclear if a cell could also use nanometer-scale components to sense micron-scale contours, such as the cytokinetic furrow and base of neuronal branches. Septins are filament-forming proteins that serve as signaling platforms and are frequently associated with areas of the plasma membrane where there is micron-scale curvature, including the cytokinetic furrow and the base of cell protrusions. We report here that fungal and human septins are able to distinguish between different degrees of micron-scale curvature in cells. By preparing supported lipid bilayers on beads of different curvature, we reconstitute and measure the intrinsic septin curvature preference. We conclude that micron-scale curvature recognition is a fundamental property of the septin cytoskeleton that provides the cell with a mechanism to know its local shape. 相似文献
687.
Modern enzymes are highly optimized biocatalysts that process their substrates with extreme efficiency. Many enzymes catalyze more than one reaction; however, the persistence of such ambiguities, their consequences and evolutionary causes are largely unknown. As a paradigmatic case, we study the history of bi-functionality for a time span of approximately two billion years for the sugar isomerase HisA from histidine biosynthesis. To look back in time, we computationally reconstructed and experimentally characterized three HisA predecessors. We show that these ancient enzymes catalyze not only the HisA reaction but also the isomerization of a similar substrate, which is commonly processed by the isomerase TrpF in tryptophan biosynthesis. Moreover, we found that three modern-day HisA enzymes from Proteobacteria and Thermotogae also possess low TrpF activity. We conclude that this bi-functionality was conserved for at least two billion years, most likely without any evolutionary pressure. Although not actively selected for, this trait can become advantageous in the case of a gene loss. Such exaptation is exemplified by the Actinobacteria that have lost the trpF gene but possess the bi-functional HisA homolog PriA, which adopts the roles of both HisA and TrpF. Our findings demonstrate that bi-functionality can perpetuate in the absence of selection for very long time-spans. 相似文献
688.
689.
Maximilian Steiner 《Plant Systematics and Evolution》1939,88(1):43-48
Zusammenfassung
Parmelia Kernstockii
Lynge et A.Zahlbr. findet sich, stellenweise häufig, auch in Nordtirol.Eine f.subglauca wird beschrieben.Die Synonymik der Art, ihre pflanzengeographische und soziologische Rolle werden kritisch besprochen. 相似文献
690.
Mahfuzur Rahman Maximilian Billmann Michael Costanzo Michael Aregger Amy H Y Tong Katherine Chan Henry N Ward Kevin R Brown Brenda J Andrews Charles Boone Jason Moffat Chad L Myers 《Molecular systems biology》2021,17(5)
We present FLEX (Functional evaluation of experimental perturbations), a pipeline that leverages several functional annotation resources to establish reference standards for benchmarking human genome‐wide CRISPR screen data and methods for analyzing them. FLEX provides a quantitative measurement of the functional information captured by a given gene‐pair dataset and a means to explore the diversity of functions captured by the input dataset. We apply FLEX to analyze data from the diverse cell line screens generated by the DepMap project. We identify a predominant mitochondria‐associated signal within co‐essentiality networks derived from these data and explore the basis of this signal. Our analysis and time‐resolved CRISPR screens in a single cell line suggest that the variable phenotypes associated with mitochondria genes across cells may reflect screen dynamics and protein stability effects rather than genetic dependencies. We characterize this functional bias and demonstrate its relevance for interpreting differential hits in any CRISPR screening context. More generally, we demonstrate the utility of the FLEX pipeline for performing robust comparative evaluations of CRISPR screens or methods for processing them. 相似文献