全文获取类型
收费全文 | 18141篇 |
免费 | 96篇 |
国内免费 | 230篇 |
专业分类
系统科学 | 384篇 |
丛书文集 | 383篇 |
教育与普及 | 74篇 |
理论与方法论 | 62篇 |
现状及发展 | 6259篇 |
研究方法 | 778篇 |
综合类 | 10005篇 |
自然研究 | 522篇 |
出版年
2014年 | 141篇 |
2013年 | 281篇 |
2012年 | 481篇 |
2011年 | 1032篇 |
2010年 | 363篇 |
2009年 | 351篇 |
2008年 | 540篇 |
2007年 | 614篇 |
2006年 | 608篇 |
2005年 | 543篇 |
2004年 | 403篇 |
2003年 | 315篇 |
2002年 | 321篇 |
2001年 | 508篇 |
2000年 | 561篇 |
1999年 | 412篇 |
1992年 | 289篇 |
1991年 | 254篇 |
1990年 | 250篇 |
1989年 | 229篇 |
1988年 | 209篇 |
1987年 | 226篇 |
1986年 | 203篇 |
1985年 | 245篇 |
1984年 | 235篇 |
1983年 | 159篇 |
1982年 | 172篇 |
1981年 | 158篇 |
1980年 | 199篇 |
1979年 | 445篇 |
1978年 | 340篇 |
1977年 | 367篇 |
1976年 | 264篇 |
1975年 | 322篇 |
1974年 | 446篇 |
1973年 | 379篇 |
1972年 | 361篇 |
1971年 | 421篇 |
1970年 | 484篇 |
1969年 | 428篇 |
1968年 | 408篇 |
1967年 | 442篇 |
1966年 | 384篇 |
1965年 | 301篇 |
1959年 | 155篇 |
1958年 | 231篇 |
1957年 | 179篇 |
1956年 | 138篇 |
1955年 | 154篇 |
1954年 | 132篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
981.
Parkinson NJ Olsson CL Hallows JL McKee-Johnson J Keogh BP Noben-Trauth K Kujawa SG Tempel BL 《Nature genetics》2001,29(1):61-65
The autosomal recessive mouse mutation quivering (qv), which arose spontaneously in 1953, produces progressive ataxia with hind limb paralysis, deafness and tremor. Six additional spontaneous alleles, qvJ, qv2J, qv3J, qv4J, qvlnd and qvlnd2J, have been identified. Ear twitch responses (Preyer's reflex) to sound are absent in homozygous qv/qv mice, although cochlear morphology seems normal and cochlear potentials recorded at the round window are no different from those of control mice. However, responses from brainstem auditory nuclei show abnormal transmission of auditory information, indicating that, in contrast to the many known mutations causing deafness originating in the cochlea, deafness in qv is central in origin. Here we report that quivering mice carry loss-of-function mutations in the mouse beta-spectrin 4 gene (Spnb4) that cause alterations in ion channel localization in myelinated nerves; this provides a rationale for the auditory and motor neuropathies of these mice. 相似文献
982.
Hollopeter G Jantzen HM Vincent D Li G England L Ramakrishnan V Yang RB Nurden P Nurden A Julius D Conley PB 《Nature》2001,409(6817):202-207
Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases. 相似文献
983.
Frequently, crop plants do not take up adequate amounts of iron from the soil, leading to chlorosis, poor yield and decreased nutritional quality. Extremely limited soil bioavailability of iron has led plants to evolve two distinct uptake strategies: chelation, which is used by the world's principal grain crops; and reduction, which is used by other plant groups. The chelation strategy involves extrusion of low-molecular-mass secondary amino acids (mugineic acids) known as 'phytosiderophores' which chelate sparingly soluble iron. The Fe(III)-phytosiderophore complex is then taken up by an unknown transporter at the root surface. The maize yellow stripe1 (ys1) mutant is deficient in Fe(III)-phytosiderophore uptake, therefore YS1 has been suggested to be the Fe(III)-phytosiderophore transporter. Here we show that ys1 is a membrane protein that mediates iron uptake. Expression of YS1 in a yeast iron uptake mutant restores growth specifically on Fe(III)-phytosiderophore media. Under iron-deficient conditions, ys1 messenger RNA levels increase in both roots and shoots. Cloning of ys1 is an important step in understanding iron uptake in grasses, and has implications for mechanisms controlling iron homeostasis in all plants. 相似文献
984.
Active zone material at the nervous system's synapses is situated next to synaptic vesicles that are docked at the presynaptic plasma membrane, and calcium channels that are anchored in the membrane. Here we use electron microscope tomography to show the arrangement and associations of structural components of this compact organelle at a model synapse, the frog's neuromuscular junction. Our findings indicate that the active zone material helps to dock the vesicles and anchor the channels, and that its architecture provides both a particular spatial relationship and a structural linkage between them. The structural linkage may include proteins that mediate the calcium-triggered exocytosis of neurotransmitter by the synaptic vesicles during synaptic transmission. 相似文献
985.
Visual abilities change over the visual field. For example, our ability to detect movement is better in peripheral vision than in foveal vision, but colour discrimination is markedly worse. The deterioration of colour vision has been attributed to reduced colour specificity in cells of the midget, parvocellular (PC) visual pathway in the peripheral retina. We have measured the colour specificity (red-green chromatic modulation sensitivity) of PC cells at eccentricities between 20 and 50 degrees in the macaque retina. Here we show that most peripheral PC cells have red-green modulation sensitivity close to that of foveal PC cells. This result is incompatible with the view that PC pathway cells in peripheral retina make indiscriminate connections ('random wiring') with retinal circuits devoted to different spectral types of cone photoreceptors. We show that selective cone connections can be maintained by dendritic field anisotropy, consistent with the morphology of PC cell dendritic fields in peripheral retina. Our results also imply that postretinal mechanisms contribute to the psychophysically demonstrated deterioration of colour discrimination in the peripheral visual field. 相似文献
986.
Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10 总被引:35,自引:0,他引:35
Chiang SH Baumann CA Kanzaki M Thurmond DC Watson RT Neudauer CL Macara IG Pessin JE Saltiel AR 《Nature》2001,410(6831):944-948
The stimulation of glucose uptake by insulin in muscle and adipose tissue requires translocation of the GLUT4 glucose transporter protein from intracellular storage sites to the cell surface. Although the cellular dynamics of GLUT4 vesicle trafficking are well described, the signalling pathways that link the insulin receptor to GLUT4 translocation remain poorly understood. Activation of phosphatidylinositol-3-OH kinase (PI(3)K) is required for this trafficking event, but it is not sufficient to produce GLUT4 translocation. We previously described a pathway involving the insulin-stimulated tyrosine phosphorylation of Cbl, which is recruited to the insulin receptor by the adapter protein CAP. On phosphorylation, Cbl is translocated to lipid rafts. Blocking this step completely inhibits the stimulation of GLUT4 translocation by insulin. Here we show that phosphorylated Cbl recruits the CrkII-C3G complex to lipid rafts, where C3G specifically activates the small GTP-binding protein TC10. This process is independent of PI(3)K, but requires the translocation of Cbl, Crk and C3G to the lipid raft. The activation of TC10 is essential for insulin-stimulated glucose uptake and GLUT4 translocation. The TC10 pathway functions in parallel with PI(3)K to stimulate fully GLUT4 translocation in response to insulin. 相似文献
987.
Preservation of ancient and fertile lithospheric mantle beneath the southwestern United States 总被引:13,自引:0,他引:13
Stable continental regions, free from tectonic activity, are generally found only within ancient cratons-the centres of continents which formed in the Archaean era, 4.0-2.5 Gyr ago. But in the Cordilleran mountain belt of western North America some younger (middle Proterozoic) regions have remained stable, whereas some older (late Archaean) regions have been tectonically disturbed, suggesting that age alone does not determine lithospheric strength and crustal stability. Here we report rhenium-osmium isotope and mineral compositions of peridotite xenoliths from two regions of the Cordilleran mountain belt. We found that the younger, undeformed Colorado plateau is underlain by lithospheric mantle that is 'depleted' (deficient in minerals extracted by partial melting of the rock), whereas the older (Archaean), yet deformed, southern Basin and Range province is underlain by 'fertile' lithospheric mantle (not depleted by melt extraction). We suggest that the apparent relationship between composition and lithospheric strength, inferred from different degrees of crustal deformation, occurs because depleted mantle is intrinsically less dense than fertile mantle (due to iron having been lost when melt was extracted from the rock). This allows the depleted mantle to form a thicker thermal boundary layer between the deep convecting mantle and the crust, thus reducing tectonic activity at the surface. The inference that not all Archaean crust developed a strong and thick thermal boundary layer leads to the possibility that such ancient crust may have been overlooked because of its intensive reworking or lost from the geological record owing to preferential recycling. 相似文献
988.
Knowledge of the seismic velocity structure at the top of the Earth's inner core is important for deciphering the physical processes responsible for inner-core growth. Previous global seismic studies have focused on structures found 100 km or deeper within the inner core, with results for the uppermost 100 km available for only isolated regions. Here we present constraints on seismic velocity variations just beneath the inner-core boundary, determined from the difference in travel time between waves reflected at the inner-core boundary and those transmitted through the inner core. We found that these travel-time residuals-observed on both global seismograph stations and several regional seismic networks-are systematically larger, by about 0.8 s, for waves that sample the 'eastern hemisphere' of the inner core (40 degrees E to 180 degrees E) compared to those that sample the 'western hemisphere' (180 degrees W to 40 degrees E). These residuals show no correlation with the angle at which the waves traverse the inner core; this indicates that seismic anisotropy is not strong in this region and that the isotropic seismic velocity of the eastern hemisphere is about 0.8% higher than that of the western hemisphere. 相似文献
989.
Phagocytosis and clearance of apoptotic cells is mediated by MER 总被引:43,自引:0,他引:43
Scott RS McMahon EJ Pop SM Reap EA Caricchio R Cohen PL Earp HS Matsushima GK 《Nature》2001,411(6834):207-211
Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had macrophages deficient in the clearance of apoptotic thymocytes. This was corrected in chimaeric mice reconstituted with bone marrow from wild-type animals. Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to be critical for the engulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus. 相似文献
990.