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221.
Vinod Sundaramoorthy Adam K. Walker Justin Yerbury Kai Ying Soo Manal A. Farg Vy Hoang Rafaa Zeineddine Damian Spencer Julie D. Atkin 《Cellular and molecular life sciences : CMLS》2013,70(21):4181-4195
Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing neurodegenerative disorder and the majority of ALS is sporadic, where misfolding and aggregation of Cu/Zn-superoxide dismutase (SOD1) is a feature shared with familial mutant-SOD1 cases. ALS is characterized by progressive neurospatial spread of pathology among motor neurons, and recently the transfer of extracellular, aggregated mutant SOD1 between cells was demonstrated in culture. However, there is currently no evidence that uptake of SOD1 into cells initiates neurodegenerative pathways reminiscent of ALS pathology. Similarly, whilst dysfunction to the ER–Golgi compartments is increasingly implicated in the pathogenesis of both sporadic and familial ALS, it remains unclear whether misfolded, wildtype SOD1 triggers ER–Golgi dysfunction. In this study we show that both extracellular, native wildtype and mutant SOD1 are taken up by macropinocytosis into neuronal cells. Hence uptake does not depend on SOD1 mutation or misfolding. We also demonstrate that purified mutant SOD1 added exogenously to neuronal cells inhibits protein transport between the ER–Golgi apparatus, leading to Golgi fragmentation, induction of ER stress and apoptotic cell death. Furthermore, we show that extracellular, aggregated, wildtype SOD1 also induces ER–Golgi pathology similar to mutant SOD1, leading to apoptotic cell death. Hence extracellular misfolded wildtype or mutant SOD1 induce dysfunction to ER–Golgi compartments characteristic of ALS in neuronal cells, implicating extracellular SOD1 in the spread of pathology among motor neurons in both sporadic and familial ALS. 相似文献
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224.
Luo Sanzhong Zhang Baolian Xian Ming Adam JaÑczuk Xie Wenhua Cheng Jinpei Peng George Wang 《科学通报(英文版)》2001,46(20):1673-1680
Lanthanide triflates are stable in water. It is possible for lanthanides to undergo many organic reactions in environmentally
friendly solvents. This makes lanthanides very promising in the field of green chemistry. This review describes the recent
development of the lanthanidecatalyzed organic reactions in protic solvents. Those reactions include Diels-Alder, Aldol, Allylation,
acetalization, pericyclization, radical reactions as well as some newlydeveloped lanthnidesbased catalysts. 相似文献
225.
Adam Morton 《Studies in history and philosophy of science》2006,37(1):114-117
226.
The nuclear envelope is a selective barrier against the movement of macromolecules between the nucleus and cytoplasm. Nuclear proteins larger than relative molecular mass 20,000-40,000 are probably actively transported across the envelope through the nuclear pore complex and are directed by specific nuclear location sequences (NLS) in the proteins. NLS mediate the nuclear import of isolated nuclear proteins after microinjection into whole cells and the nuclear accumulation of chimaeric proteins or of non-nuclear proteins conjugated to synthetic peptides. The best-characterized NLS is the simian virus 40 large T-antigen sequence. We have identified two proteins of rat liver by chemical cross-linking that interact with a synthetic peptide containing this sequence: this interaction is specific for a functional NLS, is saturable, and high affinity. The binding proteins are present in a post-mitochondrial supernatant, in nuclei and in a nuclear envelope fraction, which is consistent with a role in the transport of nuclear proteins from the cytoplasm to the nucleus. 相似文献
227.
Summary The ring-E opened dihydro derivatives of tomatidine and soladulcidine give the corresponding N-chloroamines with N-chlorosuccinimide. Treatment of these compounds with sodium methoxide yields the spiroaminoketal alkaloids, tomatidine and soladulcidine respectively, in high yields, probably via instable C=N-unsaturated intermediates which undergo spontaneous stereospecific cyclisation.
Solanum-Alkaloide. XIII. Mitteilung. XII. Mitteilung:K. Schreiber undH. Ripperger, Exper.16, 536 (1960). 相似文献
Solanum-Alkaloide. XIII. Mitteilung. XII. Mitteilung:K. Schreiber undH. Ripperger, Exper.16, 536 (1960). 相似文献
228.
Megan Chircop Chandra S. Malladi Audrey T. Lian Scott L. Page Michael Zavortink Christopher P. Gordon Adam McCluskey Phillip J. Robinson 《Cellular and molecular life sciences : CMLS》2010,67(21):3725-3737
Successful completion of cytokinesis requires the spatio-temporal regulation of protein phosphorylation and the coordinated
activity of protein kinases and phosphatases. Many mitotic protein kinases are well characterized while mitotic phosphatases
are largely unknown. Here, we show that the Ca2+- and calmodulin-dependent phosphatase, calcineurin (CaN), is required for cytokinesis in mammalian cells, functioning specifically
at the abscission stage. CaN inhibitors induce multinucleation in HeLa cells and prolong the time cells spend connected via
an extended intracellular bridge. Upon Ca2+ influx during cytokinesis, CaN is activated, targeting a set of proteins for dephosphorylation, including dynamin II (dynII).
At the intracellular bridge, phospho-dynII and CaN are co-localized to dual flanking midbody rings (FMRs) that reside on either
side of the central midbody ring. CaN activity and disassembly of the FMRs coincide with abscission. Thus, CaN activity at
the midbody plays a key role in regulating the completion of cytokinesis in mammalian cells. 相似文献
229.
Zhiliang Ma Adam Cardinal-Stakenas Youngser Park Michael W. Trosset Carey E. Priebe 《Journal of Classification》2010,27(3):307-321
We consider the problem of combining multiple dissimilarity representations via the Cartesian product of their embeddings. For concreteness, we choose the inferential task at hand to be classification. The high dimensionality of this Cartesian product space implies the necessity of dimensionality reduction before training a classifier. We propose a supervised dimensionality reduction method, which utilizes the class label information, to help achieve a favorable combination. The simulation and real data results show that our approach can improve classification accuracy compared to the alternatives of principal components analysis and no dimensionality reduction at all. 相似文献
230.
Helpers in primitively eusocial and cooperatively breeding animal societies forfeit their own reproduction to rear the offspring of a queen or breeding pair, but may eventually attain breeding status themselves. Kin selection provides a widely accepted theoretical framework for understanding these societies, but differences in genetic relatedness do not explain a universal societal feature: the huge variation between individuals in helping effort. An alternative explanation for this variation lies in a fundamental trade-off faced by helpers: by working harder, they increase the indirect component of their fitness, but simultaneously decrease their own future survival and fecundity. Here, we show that individuals work less hard when they stand to lose more future fitness through working. We experimentally manipulated two components of future fitness in social queues of hover wasps (Stenogastrinae): a helper's chance of inheriting an egg-laying position, and the workforce available to rear her offspring should she inherit. After each manipulation, helpers increased or decreased their effort as appropriate to the change in expected future fitness that they experienced. Although helping provides significant indirect fitness benefits for hover wasps, our study shows that variation in the costs associated with helping is the major determinant of helping effort. 相似文献