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The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA.  相似文献   
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Giulini A  Wang J  Jackson D 《Nature》2004,430(7003):1031-1034
Phyllotaxy describes the geometric pattern of leaves and flowers, and has intrigued botanists and mathematicians for centuries. How these patterns are initiated is poorly understood, and this is partly due to the paucity of mutants. Signalling by the plant hormone auxin appears to determine the site of leaf initiation; however, this observation does not explain how distinct patterns of phyllotaxy are initiated. abphyl1 (abph1) mutants of maize initiate leaves in a decussate pattern (that is, paired at 180 degrees), in contrast to the alternating or distichous phyllotaxy observed in wild-type maize and other grasses. Here we show that ABPH1 is homologous to two-component response regulators and is induced by the plant hormone cytokinin. ABPH1 is expressed in the embryonic shoot apical meristem, and its spatial expression pattern changes rapidly with cytokinin treatment. We propose that ABPH1 controls phyllotactic patterning by negatively regulating the cytokinin-induced expansion of the shoot meristem, thereby limiting the space available for primordium initiation at the apex.  相似文献   
14.
Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited multisystem developmental disorder characterized by growth and cognitive retardation; abnormalities of the upper limbs; gastroesophageal dysfunction; cardiac, ophthalmologic and genitourinary anomalies; hirsutism; and characteristic facial features. Genital anomalies, pyloric stenosis, congenital diaphragmatic hernias, cardiac septal defects, hearing loss and autistic and self-injurious tendencies also frequently occur. Prevalence is estimated to be as high as 1 in 10,000 (ref. 4). We carried out genome-wide linkage exclusion analysis in 12 families with CdLS and identified four candidate regions, of which chromosome 5p13.1 gave the highest multipoint lod score of 2.7. This information, together with the previous identification of a child with CdLS with a de novo t(5;13)(p13.1;q12.1) translocation, allowed delineation of a 1.1-Mb critical region on chromosome 5 for the gene mutated in CdLS. We identified mutations in one gene in this region, which we named NIPBL, in four sporadic and two familial cases of CdLS. We characterized the genomic structure of NIPBL and found that it is widely expressed in fetal and adult tissues. The fly homolog of NIPBL, Nipped-B, facilitates enhancer-promoter communication and regulates Notch signaling and other developmental pathways in Drosophila melanogaster.  相似文献   
15.
Human hybridomas secreting anti-islet autoantibodies   总被引:3,自引:0,他引:3  
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16.
Jackson JP  Lindroth AM  Cao X  Jacobsen SE 《Nature》2002,416(6880):556-560
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17.
Nonlinear grassland responses to past and future atmospheric CO(2)   总被引:17,自引:0,他引:17  
Carbon sequestration in soil organic matter may moderate increases in atmospheric CO(2) concentrations (C(a)) as C(a) increases to more than 500 micromol mol(-1) this century from interglacial levels of less than 200 micromol mol(-1) (refs 1 6). However, such carbon storage depends on feedbacks between plant responses to C(a) and nutrient availability. Here we present evidence that soil carbon storage and nitrogen cycling in a grassland ecosystem are much more responsive to increases in past C(a) than to those forecast for the coming century. Along a continuous gradient of 200 to 550 micromol mol(-1) (refs 9, 10), increased C(a) promoted higher photosynthetic rates and altered plant tissue chemistry. Soil carbon was lost at subambient C(a), but was unchanged at elevated C(a) where losses of old soil carbon offset increases in new carbon. Along the experimental gradient in C(a) there was a nonlinear, threefold decrease in nitrogen availability. The differences in sensitivity of carbon storage to historical and future C(a) and increased nutrient limitation suggest that the passive sequestration of carbon in soils may have been important historically, but the ability of soils to continue as sinks is limited.  相似文献   
18.
DNA double-strand breaks: signaling, repair and the cancer connection   总被引:38,自引:0,他引:38  
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Jackson A 《Nature》2003,424(6950):760-763
A large number of high-accuracy vector measurements of the Earth's magnetic field have recently become available from the satellite Oersted, complementing previous vector data from the satellite Magsat, which operated in 1979/80. These data can be used to infer the morphology of the magnetic field at the surface of the fluid core, approximately 2,900 km below the Earth's surface. Here I apply a new methodology to these data to calculate maps of the magnetic field at the core surface which show intense flux spots in equatorial regions. The intensity of these features is unusually large--some have intensities comparable to high-latitude flux patches near the poles, previously identified as the major component of the dynamo field. The tendency for pairing of some of these spots to the north and south of the geographical equator suggests they might be associated with the tops of equatorially symmetric columnar structures in the fluid, or their antisymmetric equivalents. The drift of the equatorial features may represent material flow or could represent wave motion; discrimination of these two effects based on future data could provide new information on the strength of the hidden toroidal magnetic field of the Earth.  相似文献   
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