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951.
Dennis Duke 《Archive for History of Exact Sciences》2009,63(6):635-654
In the Planetary Hypotheses, Ptolemy summarizes the planetary models that he discusses in great detail in the Almagest, but he changes the mean motions to account for more prolonged comparison of observations. He gives the mean motions in two
different forms: first, in terms of ‘simple, unmixed’ periods and next, in terms of ‘particular, complex’ periods, which are
approximations to linear combinations of the simple periods. As a consequence, all of the epoch values for the Moon and the
planets are different at era Philip. This is in part a consequence of the changes in the mean motions and in part due to changes
in Ptolemy’s time in the anomaly, but not the longitude or latitude, of the Moon, the mean longitude of Saturn and Jupiter,
but not Mars, and the anomaly of Venus and Mercury, the former a large change, the latter a small one. The pattern of parameter
changes we see suggests that the analyses that yielded the Planetary Hypotheses parameters were not the elegant trio analyses of the Almagest but some sort of serial determinations of the parameters based on sequences of independent observations. 相似文献
952.
953.
Lucas Matt Stylianos Michalakis Franz Hofmann Verena Hammelmann Andreas Ludwig Martin Biel Thomas Kleppisch 《Cellular and molecular life sciences : CMLS》2011,68(1):125-137
Neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate spontaneous activity, resting
membrane potential, input resistance, afterpotential, rebound activity, and dendritic integration. To evaluate the role of
HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to CA1
pyramidal cells. LTP was enhanced in mice carrying a global deletion of the channel (HCN2−/−) but not in a pyramidal neuron-restricted knockout. This precludes an influence of HCN2 located in postsynaptic pyramidal
neurons. Additionally, the selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons
in wild-type but not HCN2−/− mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells. Finally, we found
amplified LTP in the PP of mice carrying an interneuron-specific deletion of HCN2. We conclude that HCN2 channels in inhibitory
interneurons modulate synaptic plasticity in the PP by facilitating the GABAergic output onto pyramidal neurons. 相似文献
954.
L. Vanderkelen J. M. Van Herreweghe K. G. A. Vanoirbeek G. Baggerman B. Myrnes P. J. Declerck I. W. Nilsen C. W. Michiels L. Callewaert 《Cellular and molecular life sciences : CMLS》2011,68(6):1053-1064
Lysozymes are antibacterial effectors of the innate immune system in animals that hydrolyze peptidoglycan. Bacteria have evolved
protective mechanisms that contribute to lysozyme tolerance such as the production of lysozyme inhibitors, but only inhibitors
of chicken (c-) and invertebrate (i-) type lysozyme have been identified. We here report the discovery of a novel Escherichia coli inhibitor specific for goose (g-) type lysozymes, which we designate PliG (periplasmic lysozyme inhibitor of g-type lysozyme).
Although it does not inhibit c- or i-type lysozymes, PliG shares a structural sequence motif with the previously described
PliI and MliC/PliC lysozyme inhibitor families, suggesting a common ancestry and mode of action. Deletion of pliG increased the sensitivity of E. coli to g-type lysozyme. The existence of inhibitors against all major types of animal lysozyme and their contribution to lysozyme
tolerance suggest that lysozyme inhibitors may play a role in bacterial interactions with animal hosts. 相似文献
955.
Sergio Porté Agrin Moeini Irene Reche Naeem Shafqat Udo Oppermann Jaume Farrés Xavier Parés 《Cellular and molecular life sciences : CMLS》2011,68(6):1065-1077
Human ζ-crystallin is a Zn2+-lacking medium-chain dehydrogenase/reductase (MDR) included in the quinone oxidoreductase (QOR) family because of its activity
with quinones. In the present work a novel enzymatic activity was characterized: the double bond α,β-hydrogenation of medium-chain
2-alkenals and 3-alkenones. The enzyme is especially active with lipid peroxidation products such as 4-hydroxyhexenal, and
a role in their detoxification is discussed. This specificity is novel in the QOR family, and it is similar to that described
in the distantly related alkenal/one reductase family. Moreover, we report the X-ray structure of ζ-crystallin, which represents
the first structure solved for a tetrameric Zn2+-lacking MDR, and which allowed the identification of the active-site lining residues. Docking simulations suggest a role
for Tyr53 and Tyr59 in catalysis. The kinetics of Tyr53Phe and Tyr59Phe mutants support the implication of Tyr53 in binding/catalysis
of alkenal/one substrates, while Tyr59 is involved in the recognition of 4-OH-alkenals. 相似文献
956.
Jean-Pierre Vilardaga Guillermo Romero Peter A. Friedman Thomas J. Gardella 《Cellular and molecular life sciences : CMLS》2011,68(1):1-13
The parathyroid hormone (PTH) receptor type 1 (PTHR), a G protein-coupled receptor (GPCR), transmits signals to two hormone
systems—PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine—to regulate different biological processes.
PTHR responds to these hormonal stimuli by activating heterotrimeric G proteins, such as GS that stimulates cAMP production. It was thought that the PTHR, as for all other GPCRs, is only active and signals through
G proteins on the cell membrane, and internalizes into a cell to be desensitized and eventually degraded or recycled. Recent
studies with cultured cell and animal models reveal a new pathway that involves sustained cAMP signaling from intracellular
domains. Not only do these studies challenge the paradigm that cAMP production triggered by activated GPCRs originates exclusively
at the cell membrane but they also advance a comprehensive model to account for the functional differences between PTH and
PTHrP acting through the same receptor. 相似文献
957.
Eoin E. Kelly Conor P. Horgan Mary W. McCaffrey Paul Young 《Cellular and molecular life sciences : CMLS》2011,68(2):185-194
Long-term potentiation (LTP) defines persistent increases in neurotransmission strength at synapses that are triggered by
specific patterns of neuronal activity. LTP, the most widely accepted molecular model for learning, is best characterised
at glutamatergic synapses on dendritic spines. In this context, LTP involves increases in dendritic spine size and the insertion
of glutamate receptors into the post-synaptic spine membrane, which together boost post-synaptic responsiveness to neurotransmitters.
In dendrites, the material required for LTP is sourced from an organelle termed the endosomal-recycling compartment (ERC),
which is localised to the base of dendritic spines. When LTP is induced, material derived from the recycling compartment,
which contains α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptors (AMPARs), is mobilised into dendritic
spines feeding the increased need for receptors and membrane at the spine neck and head. In this review, we discuss the importance
of endosomal-recycling and the role of key proteins which control these processes in the context of LTP. 相似文献
958.
Jessica L. Slack Corey P. Causey Paul R. Thompson 《Cellular and molecular life sciences : CMLS》2011,68(4):709-720
The recent approvals of anticancer therapeutic agents targeting the histone deacetylases and DNA methyltransferases have highlighted
the important role that epigenetics plays in human diseases, and suggested that the factors controlling gene expression are
novel drug targets. Protein arginine deiminase 4 (PAD4) is one such target because its effects on gene expression parallel
those observed for the histone deacetylases. We demonstrated that F- and Cl-amidine, two potent PAD4 inhibitors, display micromolar
cytotoxic effects towards several cancerous cell lines (HL-60, MCF7 and HT-29); no effect was observed in noncancerous lines
(NIH 3T3 and HL-60 granulocytes). These compounds also induced the differentiation of HL-60 and HT29 cells. Finally, these
compounds synergistically potentiated the cell killing effects of doxorubicin. Taken together, these findings suggest PAD4
inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic
agents for this disease. 相似文献
959.
Alexander V. Zhdanov Ruslan I. Dmitriev Dmitri B. Papkovsky 《Cellular and molecular life sciences : CMLS》2011,68(5):903-917
Bafilomycin A1 (Baf) induces an elevation of cytosolic Ca2+ and acidification in neuronal cells via inhibition of the V-ATPase. Also, Baf uncouples mitochondria in differentiated PC12
(dPC12), dSH-SY5Y cells and cerebellar granule neurons, and markedly elevates their respiration. This respiratory response in dPC12 is accompanied by morphological changes in the mitochondria and decreases the mitochondrial pH, Ca2+ and ΔΨm. The response to Baf is regulated by cytosolic Ca2+ fluxes from the endoplasmic reticulum. Inhibition of permeability transition pore opening increases the depolarizing effect
of Baf on the ΔΨm. Baf induces stochastic flickering of the ΔΨm with a period of 20 ± 10 s. Under conditions of suppressed
ATP production by glycolysis, oxidative phosphorylation impaired by Baf does not provide cells with sufficient ATP levels.
Cells treated with Baf become more susceptible to excitation with KCl. Such mitochondrial uncoupling may play a role in a
number of (patho)physiological conditions induced by Baf. 相似文献
960.
Lena Dominelli 《Foundations of Science》2016,21(2):385-397
The author starts from the observation that citizenship and voluntarism are contested terms with diverse meanings. They have also been appropriated by politicians of various persuasions and imbued with meanings associated with ‘feel good’ factors that emphasize serving in a community. Therefore, voluntarism has the potential to continue the exclusion of minority groups, marginalized individuals and collective groupings at the expense of their citizenship rights, particularly those identified by Hannah Arendt as the ‘right to have rights’ that have been endorsed through public policy but today are being undermined by the ‘age of austerity’ in publicly funded welfare states. Against the background of the political context of UK, and the public rhetoric on the ‘Big Society’, the author examines whether citizenship discourses allied with voluntarism support a meaningful endorsement of altruistic solidarity or whether they endorse exploitative relationships under the guise of meeting the public needs. 相似文献