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91.
MicroRNA control of Nodal signalling 总被引:1,自引:0,他引:1
Martello G Zacchigna L Inui M Montagner M Adorno M Mamidi A Morsut L Soligo S Tran U Dupont S Cordenonsi M Wessely O Piccolo S 《Nature》2007,449(7159):183-188
MicroRNAs are crucial modulators of gene expression, yet their involvement as effectors of growth factor signalling is largely unknown. Ligands of the transforming growth factor-beta superfamily are essential for development and adult tissue homeostasis. In early Xenopus embryos, signalling by the transforming growth factor-beta ligand Nodal is crucial for the dorsal induction of the Spemann's organizer. Here we report that Xenopus laevis microRNAs miR-15 and miR-16 restrict the size of the organizer by targeting the Nodal type II receptor Acvr2a. Endogenous miR-15 and miR-16 are ventrally enriched as they are negatively regulated by the dorsal Wnt/beta-catenin pathway. These findings exemplify the relevance of microRNAs as regulators of early embryonic patterning acting at the crossroads of fundamental signalling cascades. 相似文献
92.
Bottos A Rissone A Bussolino F Arese M 《Cellular and molecular life sciences : CMLS》2011,68(16):2655-2666
The scientific interest in the family of the so-called nervous vascular parallels has been growing steadily for the past 15 years,
either by addition of new members to the group or, lately, by deepening the analysis of established concepts and mediators.
Proteins governing both neurons and vascular cells are known to be involved in events such as cell fate determination and
migration/guidance but not in the last and apparently most complex step of nervous system development, the formation and maturation
of synapses. Hence, the recent addition to this family of the specific synaptic proteins, Neurexin and Neuroligin, is a double
innovation. The two proteins, which were thought to be “simple” adhesive links between the pre- and post-synaptic sides of
chemical synapses, are in fact extremely complex and modulate the most subtle synaptic activities. We will discuss the relevant
data and the intriguing challenge of transferring synaptic activities to vascular functions. 相似文献
93.
Gharavi AG Kiryluk K Choi M Li Y Hou P Xie J Sanna-Cherchi S Men CJ Julian BA Wyatt RJ Novak J He JC Wang H Lv J Zhu L Wang W Wang Z Yasuno K Gunel M Mane S Umlauf S Tikhonova I Beerman I Savoldi S Magistroni R Ghiggeri GM Bodria M Lugani F Ravani P Ponticelli C Allegri L Boscutti G Frasca G Amore A Peruzzi L Coppo R Izzi C Viola BF Prati E Salvadori M Mignani R Gesualdo L Bertinetto F Mesiano P Amoroso A Scolari F Chen N Zhang H Lifton RP 《Nature genetics》2011,43(4):321-327
We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 × 10?2? and 4.84 × 10?? and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures. 相似文献
94.
Defective planar cell polarity in polycystic kidney disease 总被引:15,自引:0,他引:15
Fischer E Legue E Doyen A Nato F Nicolas JF Torres V Yaniv M Pontoglio M 《Nature genetics》2006,38(1):21-23
Morphogenesis involves coordinated proliferation, differentiation and spatial distribution of cells. We show that lengthening of renal tubules is associated with mitotic orientation of cells along the tubule axis, demonstrating intrinsic planar cell polarization, and we demonstrate that mitotic orientations are significantly distorted in rodent polycystic kidney models. These results suggest that oriented cell division dictates the maintenance of constant tubule diameter during tubular lengthening and that defects in this process trigger renal tubular enlargement and cyst formation. 相似文献
95.
François Viète is considered the father both of modern algebra and of modern cryptanalysis. The paper outlines Viète’s major contributions in these two mathematical fields and argues that, despite an obvious parallel between them, there is an essential difference. Viète’s ‘new algebra’ relies on his reform of the classical method of analysis and synthesis, in particular on a new conception of analysis and the introduction of a new formalism. The procedures he suggests to decrypt coded messages are particular forms of analysis based on the use of formal methods. However, Viète’s algebraic analysis is not an analysis in the same sense as his cryptanalysis is. In Aristotelian terms, the first is a form of ‘’, while the second is a form of . While the first is a top-down argument from the point of view of the human subject, since it is an argument going from what is not actual to what is actual for such a subject, the second one is a bottom-up argument from this same point of view, since it starts from what is first for us and proceed towards what is first by nature. 相似文献
96.
We reconstruct essential features of Lagrange’s theory of analytical functions by exhibiting its structure and basic assumptions,
as well as its main shortcomings. We explain Lagrange’s notions of function and algebraic quantity, and we concentrate on
power-series expansions, on the algorithm for derivative functions, and the remainder theorem—especially on the role this
theorem has in solving geometric and mechanical problems. We thus aim to provide a better understanding of Enlightenment mathematics
and to show that the foundations of mathematics did not, for Lagrange, concern the solidity of its ultimate bases, but rather
purity of method—the generality and internal organization of the discipline. 相似文献
97.
Sarno S Mazzorana M Traynor R Ruzzene M Cozza G Pagano MA Meggio F Zagotto G Battistutta R Pinna LA 《Cellular and molecular life sciences : CMLS》2012,69(3):449-460
8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of
protein kinase CK2 (Ki = 0.22 μM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter
as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as
“denitro NBC”, dNBC), the inhibitory power toward CK2 is almost entirely lost (IC50 > 30 μM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases
that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC50 values with NBC and dNBC are 15 and 0.60 μM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent
inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural
features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit
of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68
and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved
water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to
the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A
by dNBC. 相似文献
98.
Elisa Bisicchia Valerio Chiurchiù Maria Teresa Viscomi Laura Latini Filomena Fezza Luca Battistini Mauro Maccarrone Marco Molinari 《Cellular and molecular life sciences : CMLS》2013,70(12):2191-2204
Endocannabinoids (eCBs) and glucocorticoids (GCs) are two distinct classes of signaling lipids that exert both neuroprotective and immunosuppressive effects; however, the possibility of an actual interaction of their receptors [i.e., type-2 cannabinoid (CB2) and glucocorticoid receptor α (GRα), respectively] remains unexplored. Here, we demonstrate that the concomitant activation of CB2 and GRα abolishes the neuroprotective effects induced by each receptor on central neurons and on glial cells in animal models of remote cell death. We also show that the ability of eCBs and GCs, used individually, to inhibit tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production from activated human T lymphocytes is lost when CB2 and GRα are activated simultaneously. In addition, signal transduction pathways triggered by concomitant activation of both receptors led to increased levels of GRβ, heat-shock proteins-70 and -90, and p-JNK, as well as to reduced levels of p-STAT6. These effects were reversed only by selectively antagonizing CB2, but not GRα. Overall, our study demonstrates for the first time the existence of a CB2-driven negative cross-talk between eCB and GC signaling in both rats and humans, thus paving the way to the possible therapeutic exploitation of CB2 as a new target for chronic inflammatory and neurodegenerative diseases. 相似文献
99.
A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures 总被引:1,自引:0,他引:1
Sharp AJ Mefford HC Li K Baker C Skinner C Stevenson RE Schroer RJ Novara F De Gregori M Ciccone R Broomer A Casuga I Wang Y Xiao C Barbacioru C Gimelli G Bernardina BD Torniero C Giorda R Regan R Murday V Mansour S Fichera M Castiglia L Failla P Ventura M Jiang Z Cooper GM Knight SJ Romano C Zuffardi O Chen C Schwartz CE Eichler EE 《Nature genetics》2008,40(3):322-328
We report a recurrent microdeletion syndrome causing mental retardation, epilepsy and variable facial and digital dysmorphisms. We describe nine affected individuals, including six probands: two with de novo deletions, two who inherited the deletion from an affected parent and two with unknown inheritance. The proximal breakpoint of the largest deletion is contiguous with breakpoint 3 (BP3) of the Prader-Willi and Angelman syndrome region, extending 3.95 Mb distally to BP5. A smaller 1.5-Mb deletion has a proximal breakpoint within the larger deletion (BP4) and shares the same distal BP5. This recurrent 1.5-Mb deletion contains six genes, including a candidate gene for epilepsy (CHRNA7) that is probably responsible for the observed seizure phenotype. The BP4-BP5 region undergoes frequent inversion, suggesting a possible link between this inversion polymorphism and recurrent deletion. The frequency of these microdeletions in mental retardation cases is approximately 0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes. 相似文献
100.