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排序方式: 共有204条查询结果,搜索用时 15 毫秒
81.
82.
D G Shu S C Morris J Han L Chen X L Zhang Z F Zhang H Q Liu Y Li J N Liu 《Nature》2001,414(6862):419-424
Cambrian fossil-Lagerst?tten (sites of exceptional fossil preservation), such as those from Chengjiang (Lower Cambrian) and the Burgess Shale (Middle Cambrian), provide our best window into the Cambrian 'explosion'. Such faunas are known from about 40 localities, and have yielded a widely disparate series of taxa ranging from ctenophores to agnathan fish. Recent excavations of the Chengjiang fossil-Lagerst?tte, known from a series of sites near Kunming in Yunnan, south China, have resulted in the discovery of several new forms. In conjunction with material described earlier, these provide evidence for a new group of metazoans, the vetulicolians. Several features, notably a series of gill slits, suggest that this group can throw light on an early stage of deuterostome diversification. 相似文献
83.
Deshayes S Morris MC Divita G Heitz F 《Cellular and molecular life sciences : CMLS》2005,62(16):1839-1849
The main problem of therapeutic efficiency lies in the crossing of cellular membranes. Therefore, significant effort is being made to develop agents which can cross these barriers and deliver therapeutic agents into cellular compartments. In recent years, a large amount of data on the use of peptides as delivery agents has accumulated. Several groups have published the first positive results using peptides for the delivery of therapeutic agents in relevant animal models. These peptides, called cell-penetrating peptides (CPPs), are short peptides (fewer than 30 residues) with a net positive charge and acting in a receptor- and energy-independent manner. Here, we give an extensive review of peptide-mediated delivery systems and discuss their applications, with particular focus on the mechanisms leading to cellular internalization.Received 14 March 2005; received after revision 25 April 2005; accepted 28 April 2005 相似文献
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Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis 总被引:1,自引:0,他引:1
Glasson SS Askew R Sheppard B Carito B Blanchet T Ma HL Flannery CR Peluso D Kanki K Yang Z Majumdar MK Morris EA 《Nature》2005,434(7033):644-648
Human osteoarthritis is a progressive disease of the joints characterized by degradation of articular cartilage. Although disease initiation may be multifactorial, the cartilage destruction appears to be a result of uncontrolled proteolytic extracellular matrix destruction. A major component of the cartilage extracellular matrix is aggrecan, a proteoglycan that imparts compressive resistance to the tissue. Aggrecan is cleaved at a specific 'aggrecanase' site in human osteoarthritic cartilage; this cleavage can be performed by several members of ADAMTS family of metalloproteases. The relative contribution of individual ADAMTS proteases to cartilage destruction during osteoarthritis has not been resolved. Here we describe experiments with a genetically modified mouse in which the catalytic domain of ADAMTS5 (aggrecanase-2) was deleted. After surgically induced joint instability, there was significant reduction in the severity of cartilage destruction in the ADAMTS5 knockout mice compared with wild-type mice. This is the first report of a single gene deletion capable of abrogating the course of cartilage destruction in an animal model of osteoarthritis. These results demonstrate that ADAMTS5 is the primary 'aggrecanase' responsible for aggrecan degradation in a murine model of osteoarthritis, and suggest rational strategies for therapeutic intervention in osteoarthritis. 相似文献
87.
Growth of human breast cancer cells inhibited by a luteinizing hormone-releasing hormone agonist 总被引:6,自引:0,他引:6
About one-third of human breast cancers require hormones for their continued growth and endocrine ablation or anti-hormone therapy can cause regression of these tumours. As a consequence, ovariectomy in premenopausal women or administration of an anti-oestrogen (tamoxifen) in postmenopausal women represent major options for treatment of metastatic breast cancer. Alternatively, chronic administration of agonistic analogues of luteinizing hormone-releasing hormone (LHRH) causes regression of mammary tumours in experimental animals, and such treatment has shown promise in a small series of premenopausal women with advanced breast cancer. It has been assumed that these results were achieved by suppressing the pituitary-ovarian axis, as the treatment causes a reduction in circulating levels of gonadal steroids similar to that produced by castration. However, LHRH agonists can exert major effects on tissues other than the pituitary in animals and in the human. Such findings, coupled with reports of LHRH in human breast milk and immunohistochemical evidence for the presence of LHRH-like activity in some human breast tumours, prompted us to test whether LHRH agonists could have direct antitumour effects. We now report major direct effects of LHRH and its agonists on the growth of breast tumour cells in culture. 相似文献
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The subducted component in island arc lavas: constraints from Be isotopes and B-Be systematics 总被引:6,自引:0,他引:6
Although high concentrations of beryllium-10 and boron are taken as unequivocal indicators of the contribution of subducting plates, controversy persists about the processes by which material is transferred from slabs to the sources of arc magmas. Data on (10)Be/Be and B/Be ratios from four arcs suggest that the contribution from the slab is compositionally homogeneous in each arc and that subducted boron is not stored in the sub-arc mantle. The link between subduction and magma-tism at convergent margins seems to be well regulated. 相似文献
90.
Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. 总被引:15,自引:0,他引:15
A R Curtis C Fey C M Morris L A Bindoff P G Ince P F Chinnery A Coulthard M J Jackson A P Jackson D P McHale D Hay W A Barker A F Markham D Bates A Curtis J Burn 《Nature genetics》2001,28(4):350-354
We describe here a previously unknown, dominantly inherited, late-onset basal ganglia disease, variably presenting with extrapyramidal features similar to those of Huntington's disease (HD) or parkinsonism. We mapped the disorder, by linkage analysis, to 19q13.3, which contains the gene for ferritin light polypeptide (FTL). We found an adenine insertion at position 460-461 that is predicted to alter carboxy-terminal residues of the gene product. Brain histochemistry disclosed abnormal aggregates of ferritin and iron. Low serum ferritin levels also characterized patients. Ferritin, the main iron storage protein, is composed of 24 subunits of two types (heavy, H and light, L) which form a soluble, hollow sphere. Brain iron deposition increases normally with age, especially in the basal ganglia, and is a suspected causative factor in several neurodegenerative diseases in which it correlates with visible pathology, possibly by its involvement in toxic free-radical reactions. We found the same mutation in five apparently unrelated subjects with similar extrapyramidal symptoms. An abnormality in ferritin strongly indicates a primary function for iron in the pathogenesis of this new disease, for which we propose the name 'neuroferritinopathy'. 相似文献