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101.
102.
Silvia Bassani Alessandra Folci Jonathan Zapata Maria Passafaro 《Cellular and molecular life sciences : CMLS》2013,70(23):4411-4430
Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate most fast excitatory synaptic transmission in the central nervous system. The content and composition of AMPARs in postsynaptic membranes (which determine synaptic strength) are dependent on the regulated trafficking of AMPAR subunits in and out of the membranes. AMPAR trafficking is a key mechanism that drives nascent synapse development, and is the main determinant of both Hebbian and homeostatic plasticity in mature synapses. Hebbian plasticity seems to be the biological substrate of at least some forms of learning and memory; while homeostatic plasticity (also known as synaptic scaling) keeps neuronal circuits stable by maintaining changes within a physiological range. In this review, we examine recent findings that provide further understanding of the role of AMPAR trafficking in synapse maturation, Hebbian plasticity, and homeostatic plasticity. 相似文献
103.
Kittler R Putz G Pelletier L Poser I Heninger AK Drechsel D Fischer S Konstantinova I Habermann B Grabner H Yaspo ML Himmelbauer H Korn B Neugebauer K Pisabarro MT Buchholz F 《Nature》2004,432(7020):1036-1040
RNA interference (RNAi) is an evolutionarily conserved defence mechanism whereby genes are specifically silenced through degradation of messenger RNAs; this process is mediated by homologous double-stranded (ds)RNA molecules. In invertebrates, long dsRNAs have been used for genome-wide screens and have provided insights into gene functions. Because long dsRNA triggers a nonspecific interferon response in many vertebrates, short interfering (si)RNA or short hairpin (sh)RNAs must be used for these organisms to ensure specific gene silencing. Here we report the generation of a genome-scale library of endoribonuclease-prepared short interfering (esi)RNAs from a sequence-verified complementary DNA collection representing 15,497 human genes. We used 5,305 esiRNAs from this library to screen for genes required for cell division in HeLa cells. Using a primary high-throughput cell viability screen followed by a secondary high content videomicroscopy assay, we identified 37 genes required for cell division. These include several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown. Thus, our study uncovers new aspects of cell division and establishes esiRNA as a versatile approach for genomic RNAi screens in mammalian cells. 相似文献
104.
Genome sequencing in microfabricated high-density picolitre reactors 总被引:21,自引:0,他引:21
Margulies M Egholm M Altman WE Attiya S Bader JS Bemben LA Berka J Braverman MS Chen YJ Chen Z Dewell SB Du L Fierro JM Gomes XV Godwin BC He W Helgesen S Ho CH Ho CH Irzyk GP Jando SC Alenquer ML Jarvie TP Jirage KB Kim JB Knight JR Lanza JR Leamon JH Lefkowitz SM Lei M Li J Lohman KL Lu H Makhijani VB McDade KE McKenna MP Myers EW Nickerson E Nobile JR Plant R Puc BP Ronan MT Roth GT Sarkis GJ Simons JF Simpson JW Srinivasan M Tartaro KR Tomasz A Vogt KA Volkmer GA Wang SH Wang Y Weiner MP 《Nature》2005,437(7057):376-380
The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine. 相似文献
105.
Gandin V Miluzio A Barbieri AM Beugnet A Kiyokawa H Marchisio PC Biffo S 《Nature》2008,455(7213):684-688
Cell growth and proliferation require coordinated ribosomal biogenesis and translation. Eukaryotic initiation factors (eIFs) control translation at the rate-limiting step of initiation. So far, only two eIFs connect extracellular stimuli to global translation rates: eIF4E acts in the eIF4F complex and regulates binding of capped messenger RNA to 40S subunits, downstream of growth factors, and eIF2 controls loading of the ternary complex on the 40S subunit and is inhibited on stress stimuli. No eIFs have been found to link extracellular stimuli to the activity of the large 60S ribosomal subunit. eIF6 binds 60S ribosomes precluding ribosome joining in vitro. However, studies in yeasts showed that eIF6 is required for ribosome biogenesis rather than translation. Here we show that mammalian eIF6 is required for efficient initiation of translation, in vivo. eIF6 null embryos are lethal at preimplantation. Heterozygous mice have 50% reduction of eIF6 levels in all tissues, and show reduced mass of hepatic and adipose tissues due to a lower number of cells and to impaired G1/S cell cycle progression. eIF6(+/-) cells retain sufficient nucleolar eIF6 and normal ribosome biogenesis. The liver of eIF6(+/-) mice displays an increase of 80S in polysomal profiles, indicating a defect in initiation of translation. Consistently, isolated hepatocytes have impaired insulin-stimulated translation. Heterozygous mouse embryonic fibroblasts recapitulate the organism phenotype and have normal ribosome biogenesis, reduced insulin-stimulated translation, and delayed G1/S phase progression. Furthermore, eIF6(+/-) cells are resistant to oncogene-induced transformation. Thus, eIF6 is the first eIF associated with the large 60S subunit that regulates translation in response to extracellular signals. 相似文献
106.
Emma Langella Martina Buonanno Daniela Vullo Nina Dathan Marilisa Leone Claudiu T. Supuran Giuseppina De Simone Simona Maria Monti 《Cellular and molecular life sciences : CMLS》2018,75(17):3283-3296
Human carbonic anhydrase IX (hCA IX) is a tumour-associated enzyme present in a limited number of normal tissues, but overexpressed in several malignant human tumours. It is a transmembrane protein, where the extracellular region consists of a greatly investigated catalytic CA domain and a much less investigated proteoglycan-like (PG) domain. Considering its important role in tumour biology, here, we report for the first time the full characterization of the PG domain, providing insights into its structural and functional features. In particular, this domain has been produced at high yields in bacterial cells and characterized by means of biochemical, biophysical and molecular dynamics studies. Results show that it belongs to the family of intrinsically disordered proteins, being globally unfolded with only some local residual polyproline II secondary structure. The observed conformational flexibility may have several important roles in tumour progression, facilitating interactions of hCA IX with partner proteins assisting tumour spreading and progression. 相似文献
107.
Maria Luiza Beçak Kazumi Fukuda Pizzocaro 《Cellular and molecular life sciences : CMLS》1980,36(2):164-166
Summary Previtellogenic oocytes ofOdontophrynus americanus display hundreds of chromatin circles. Electron microscopy of spread preparations of isolated nuclei shows that the circles originate from the chromatin. The circles change their morphology and form new copies. The length of the DNA packed in the nucleosomal circles is about 2.5–3.5 m or multiples of this value. Assuming that histones need not be removed from chromatin before DNA replication3 we suggest that the circles might belong to the process of rDNA amplification.This work was supported by grants from the Brazilian CNPq, FAPESP and FEDIB.We thank Dr A. Brunner Jr for the use of the electron microscope and Dr N. Leon for his valuable help. 相似文献
108.
Serena Duchi Valeria Cavaliere Luca Fagnocchi Maria Rosaria Grimaldi Patrizia Falabella Franco Graziani Silvia Gigliotti Francesco Pennacchio Giuseppe Gargiulo 《Cellular and molecular life sciences : CMLS》2010,67(10):1699-1712
Polydnavirus-encoded IκB-like proteins are similar to insect and mammalian IκB, and an immunosuppressive function in the host
cells has been inferred to these proteins. Here we show that the expression of one of these IκB-like viral genes, the TnBVank1, in the Drosophila germline affects the localization of gurken, bicoid, and oskar mRNAs whose gene products are relevant for proper embryonic patterning. The altered localization of these mRNAs is suggestive
of general defects in the intracellular, microtubule-based, trafficking routes. Analysis of microtubule motor proteins components
such as the dynein heavy chain and the kinesin heavy chain revealed defects in the polarized microtubule network. Interestingly,
the TnBVANK1 viral protein is uniformly distributed over the entire oocyte cortex, and appears to be anchored to the microtubule
ends. Our data open up a very interesting issue on novel function(s) played by the ank gene family by interfering with cytoskeleton organization. 相似文献
109.
Marcos Leandro Hoffmann Souza Luis Henrique Rodrigues Maria Isabel Wolf Motta Morandi 《Systemic Practice and Action Research》2018,31(1):87-104
The growth of the petrochemical industry is based on end-user applications such as the automotive and construction sectors, which are the main drivers of the styrene market. However, the use of substitutes for petrochemicals is a reality and creates a competition in the applications of petroleum products. In this sense, this research aimed to design a system dynamics model to evaluate different scenarios, observing the behavior of the styrene demand over time. In the first phase of the project, a greater understanding of the issue was created and a closed loops diagram was elaborated. It was used during the second phase to design an explanatory regression validation model for the styrene demand. In phase three, a visualizing model and scenarios were designed. The scenarios themselves and the results of each scenario were evaluated. The designed and simulated scenarios aimed to evaluate the impact that the use of substitute materials and the variations in gross domestic product cause to the styrene market. The use of system dynamics together with scenario planning was efficient as different strategies for the market could be evaluated based on the simulated scenarios. A critical analysis of the model’s contribution to the decision-making within organizations concludes the study. 相似文献
110.
Francesca Cherubino Andreea Miszner Maria Daniela Renna Rachele Sangaletti Stefano Giovannardi Elena Bossi 《Cellular and molecular life sciences : CMLS》2009,66(23):3797-3808
The effects of three tricyclic antidepressants (TCAs) and two serotonin selective reuptake inhibitors (SSRIs) have been studied
with an electrophysiological approach on Xenopus laevis oocytes expressing the rat GABA (γ-Aminobutyric-acid) transporter rGAT1. All tested TCAs and SSRIs inhibit the GABA-associated
current in a dose-dependent way with low but comparable efficacy. The pre-steady-state and uncoupled currents appear substantially
unaffected. The efficacy of desipramine, but not of the other drugs, is strongly increased in the lysine-glutamate or -aspartate
mutants K448E and K448D. Comparison of I
max and K
0.5GABA in the absence and presence of desipramine showed that both parameters are reduced by the drug in the wild-type and in the
K448E mutant. This suggests an uncompetitive inhibition, in which the drug can bind only after the substrate, an explanation
in agreement with the lack of effects on the pre-steady-state and leak currents, and with the known structural data. 相似文献