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181.
Hattar S Lucas RJ Mrosovsky N Thompson S Douglas RH Hankins MW Lem J Biel M Hofmann F Foster RG Yau KW 《Nature》2003,424(6944):76-81
In the mammalian retina, besides the conventional rod-cone system, a melanopsin-associated photoreceptive system exists that conveys photic information for accessory visual functions such as pupillary light reflex and circadian photo-entrainment. On ablation of the melanopsin gene, retinal ganglion cells that normally express melanopsin are no longer intrinsically photosensitive. Furthermore, pupil reflex, light-induced phase delays of the circadian clock and period lengthening of the circadian rhythm in constant light are all partially impaired. Here, we investigated whether additional photoreceptive systems participate in these responses. Using mice lacking rods and cones, we measured the action spectrum for phase-shifting the circadian rhythm of locomotor behaviour. This spectrum matches that for the pupillary light reflex in mice of the same genotype, and that for the intrinsic photosensitivity of the melanopsin-expressing retinal ganglion cells. We have also generated mice lacking melanopsin coupled with disabled rod and cone phototransduction mechanisms. These animals have an intact retina but fail to show any significant pupil reflex, to entrain to light/dark cycles, and to show any masking response to light. Thus, the rod-cone and melanopsin systems together seem to provide all of the photic input for these accessory visual functions. 相似文献
182.
183.
全书分为四部分,含19章1个附录。第一部分单质点的牛顿力学,含第1~8章。第1章代数和向量的运算;第2章速度、加速度和标量角速展;第3章牛顿运动定律和引力定律;第4章质点动力学中的问题;第5章线性振荡;第6章能量守恒;第7章有心场中的轨迹;第8章非线性振荡和相空间。第二部分多质点系统,含9~11章。第9章能量原理;第10章线性动量原理;第11章角动量原理。第三部分分析力学,含第12~14章。第12章拉格朗日方程和守恒原理;第13章变分的运算和哈密顿原理;第14章哈密顿方程和相空间。第四部分进一步的论题,含第15~19章。第15章小振荡的一般方程;第16章向量角速度和刚体运动学;第17章旋转参考标架;第18章张量代数和惯性张量;第19章刚体动力学中的问题。附录质量中心和惯性矩。最后对每一章后的习题给出了部分的解答。 相似文献
184.
185.
Ravikumar B Vacher C Berger Z Davies JE Luo S Oroz LG Scaravilli F Easton DF Duden R O'Kane CJ Rubinsztein DC 《Nature genetics》2004,36(6):585-595
Huntington disease is one of nine inherited neurodegenerative disorders caused by a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate abnormally in intracellular aggregates. Here we show that mammalian target of rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models, transgenic mice and human brains. Sequestration of mTOR impairs its kinase activity and induces autophagy, a key clearance pathway for mutant huntingtin fragments. This protects against polyglutamine toxicity, as the specific mTOR inhibitor rapamycin attenuates huntingtin accumulation and cell death in cell models of Huntington disease, and inhibition of autophagy has the converse effects. Furthermore, rapamycin protects against neurodegeneration in a fly model of Huntington disease, and the rapamycin analog CCI-779 improved performance on four different behavioral tasks and decreased aggregate formation in a mouse model of Huntington disease. Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease. 相似文献
186.
Climate varied enormously over the most recent ice age--for example, large pulses of ice-rafted debris, originating mainly from the Labrador Sea, were deposited into the North Atlantic at roughly 7,000-year intervals, with global climatic implications. Here we show that ocean tides within the Labrador Sea were exceptionally large over the period spanning these huge, abrupt ice movements, which are known as Heinrich events. We propose that tides played a catalytic role in liberating iceberg armadas during that time. 相似文献
187.
Tschumperlin DJ Dai G Maly IV Kikuchi T Laiho LH McVittie AK Haley KJ Lilly CM So PT Lauffenburger DA Kamm RD Drazen JM 《Nature》2004,429(6987):83-86
Physical forces elicit biochemical signalling in a diverse array of cells, tissues and organisms, helping to govern fundamental biological processes. Several hypotheses have been advanced that link physical forces to intracellular signalling pathways, but in many cases the molecular mechanisms of mechanotransduction remain elusive. Here we find that compressive stress shrinks the lateral intercellular space surrounding epithelial cells, and triggers cellular signalling via autocrine binding of epidermal growth factor family ligands to the epidermal growth factor receptor. Mathematical analysis predicts that constant rate shedding of autocrine ligands into a collapsing lateral intercellular space leads to increased local ligand concentrations that are sufficient to account for the observed receptor signalling; direct experimental comparison of signalling stimulated by compressive stress versus exogenous soluble ligand supports this prediction. These findings establish a mechanism by which mechanotransduction arises from an autocrine ligand-receptor circuit operating in a dynamically regulated extracellular volume, not requiring induction of force-dependent biochemical processes within the cell or cell membrane. 相似文献
188.
Bleaching patterns in reef corals 总被引:3,自引:0,他引:3
189.
Evolution of genes and genomes on the Drosophila phylogeny 总被引:2,自引:0,他引:2
Drosophila Genomes Consortium Clark AG Eisen MB Smith DR Bergman CM Oliver B Markow TA Kaufman TC Kellis M Gelbart W Iyer VN Pollard DA Sackton TB Larracuente AM Singh ND Abad JP Abt DN Adryan B Aguade M Akashi H Anderson WW Aquadro CF Ardell DH Arguello R Artieri CG Barbash DA Barker D Barsanti P Batterham P Batzoglou S Begun D Bhutkar A Blanco E Bosak SA Bradley RK Brand AD Brent MR Brooks AN Brown RH Butlin RK Caggese C Calvi BR Bernardo de Carvalho A Caspi A Castrezana S Celniker SE 《Nature》2007,450(7167):203-218
Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species. 相似文献
190.