全文获取类型
收费全文 | 177篇 |
免费 | 0篇 |
专业分类
系统科学 | 2篇 |
教育与普及 | 1篇 |
现状及发展 | 21篇 |
研究方法 | 13篇 |
综合类 | 137篇 |
自然研究 | 3篇 |
出版年
2021年 | 1篇 |
2012年 | 8篇 |
2011年 | 8篇 |
2008年 | 4篇 |
2007年 | 6篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 8篇 |
2001年 | 5篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1970年 | 7篇 |
1969年 | 3篇 |
1968年 | 7篇 |
1967年 | 6篇 |
1965年 | 3篇 |
1963年 | 1篇 |
排序方式: 共有177条查询结果,搜索用时 15 毫秒
101.
Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man 总被引:63,自引:0,他引:63
H H Kazazian C Wong H Youssoufian A F Scott D G Phillips S E Antonarakis 《Nature》1988,332(6160):164-166
102.
The scid mutation in mice causes a general defect in DNA repair 总被引:62,自引:0,他引:62
Mice homozygous for the scid mutation on chromosome 16 have a severe combined immune deficiency as a result of their inability to correctly rearrange their immunoglobulin and T-cell receptor genes. In scid mice, when precursors for B and T lymphocytes reach the stage of development requiring expression of these surface receptors, a defective recombinase system aberrantly cuts and rejoins the receptor gene segments greatly reducing the efficiency of producing functional receptors. As a result, most scid mice have no detectable B or T lymphocytes. We have demonstrated that the scid defect is not specific to lymphocyte development. Myeloid cells and fibroblasts from scid mice show a marked increase in sensitivity to ionizing radiation, indicating that the scid mutation leads to an inability to repair DNA damage induced by ionizing radiation as well as interfering with rearrangement of the immunoglobulin and T-cell receptor genes. 相似文献
103.
104.
105.
Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway 总被引:1,自引:0,他引:1
Bulavin DV Phillips C Nannenga B Timofeev O Donehower LA Anderson CW Appella E Fornace AJ 《Nature genetics》2004,36(4):343-350
Modulation of tumor suppressor activities may provide new opportunities for cancer therapy. Here we show that disruption of the gene Ppm1d encoding Wip1 phosphatase activated the p53 and p16 (also called Ink4a)-p19 (also called ARF) pathways through p38 MAPK signaling and suppressed in vitro transformation of mouse embryo fibroblasts (MEFs) by oncogenes. Disruption of the gene Cdkn2a (encoding p16 and p19), but not of Trp53 (encoding p53), reconstituted cell transformation in Ppm1d-null MEFs. In vivo, deletion of Ppm1d in mice bearing mouse mammary tumor virus (MMTV) promoter-driven oncogenes Erbb2 (also called c-neu) or Hras1 impaired mammary carcinogenesis, whereas reduced expression of p16 and p19 by methylation-induced silencing or inactivation of p38 MAPK correlated with tumor appearance. We conclude that inactivation or depletion of the Wip1 phosphatase with resultant p38 MAPK activation suppresses tumor appearance by modulating the Cdkn2a tumor-suppressor locus. 相似文献
106.
Role of CO2 in the formation of gold deposits 总被引:6,自引:0,他引:6
Much of global gold production has come from deposits with uneconomic concentrations of base metals, such as copper, lead and zinc. These 'gold-only' deposits are thought to have formed from hot, aqueous fluids rich in carbon dioxide, but only minor significance has been attached to the role of the CO2 in the process of gold transport. This is because chemical bonding between gold ions and CO2 species is not strong, and so it is unlikely that CO2 has a direct role in gold transport. An alternative indirect role for CO2 as a weak acid that buffers pH has also appeared unlikely, because previously inferred pH values for such gold-bearing fluids are variable. Here we show that such calculated pH values are unlikely to record conditions of gold transport, and propose that CO2 may play a critical role during gold transport by buffering the fluid in a pH range where elevated gold concentration can be maintained by complexation with reduced sulphur. Our conclusions, which are supported by geochemical modelling, may provide a platform for new gold exploration methods. 相似文献
107.
Migratory birds are known to use the geomagnetic field as a source of compass information. There are two competing hypotheses for the primary process underlying the avian magnetic compass, one involving magnetite, the other a magnetically sensitive chemical reaction. Here we show that oscillating magnetic fields disrupt the magnetic orientation behaviour of migratory birds. Robins were disoriented when exposed to a vertically aligned broadband (0.1-10 MHz) or a single-frequency (7-MHz) field in addition to the geomagnetic field. Moreover, in the 7-MHz oscillating field, this effect depended on the angle between the oscillating and the geomagnetic fields. The birds exhibited seasonally appropriate migratory orientation when the oscillating field was parallel to the geomagnetic field, but were disoriented when it was presented at a 24 degrees or 48 degrees angle. These results are consistent with a resonance effect on singlet-triplet transitions and suggest a magnetic compass based on a radical-pair mechanism. 相似文献
108.
Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2 总被引:12,自引:0,他引:12
Coste SC Kesterson RA Heldwein KA Stevens SL Heard AD Hollis JH Murray SE Hill JK Pantely GA Hohimer AR Hatton DC Phillips TJ Finn DA Low MJ Rittenberg MB Stenzel P Stenzel-Poore MP 《Nature genetics》2000,24(4):403-409
The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine and behavioural responses to stress, and the related hormone urocortin (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2. These receptors may exhibit distinct functions due to unique tissue distribution and pharmacology. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses. Here we generate Crhr2-/- mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2-/- mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2-/- mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2-/- mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2-/- mice following Ucn, but Crhr2-/- mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2-/- mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2-/- mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2. 相似文献
109.
Immune control of HIV-1 after early treatment of acute infection 总被引:66,自引:0,他引:66
Rosenberg ES Altfeld M Poon SH Phillips MN Wilkes BM Eldridge RL Robbins GK D'Aquila RT Goulder PJ Walker BD 《Nature》2000,407(6803):523-526
Virus-specific T-helper cells are considered critical for the control of chronic viral infections. Successful treatment of acute HIV-1 infection leads to augmentation of these responses, but whether this enhances immune control has not been determined. We administered one or two supervised treatment interruptions to eight subjects with treated acute infection, with the plan to restart therapy if viral load exceeded 5,000 copies of HIV-1 RNA per millilitre of plasma (the level at which therapy has been typically recommended) for three consecutive weeks, or 50,000 RNA copies per ml at one time. Here we show that, despite rebound in viraemia, all subjects were able to achieve at least a transient steady state off therapy with viral load below 5,000 RNA copies per ml. At present, five out of eight subjects remain off therapy with viral loads of less than 500 RNA copies per ml plasma after a median 6.5 months (range 5-8.7 months). We observed increased virus-specific cytotoxic T lymphocytes and maintained T-helper-cell responses in all. Our data indicate that functional immune responses can be augmented in a chronic viral infection, and provide rationale for immunotherapy in HIV-1 infection. 相似文献
110.
Vaccinia virus recombinants that express cloned genes encoding antigens of unrelated infectious agents, such as hepatitis B virus and human immunodeficiency virus (HIV), provide a new approach to the development of live vaccines. Although there is evidence that genetically engineered vaccinia viruses have reduced pathogenicity a major obstacle to their use as vaccines is that severe complications can occur after vaccination, especially in immunodeficient individuals. We describe here a recombinant vaccinia virus expressing murine interleukin-2 (IL-2) and show that athymic nude mice infected with the recombinant virus resolve the virus infection rapidly whereas mice infected with control virus develop a progressive vaccinal disease. By incorporating the gene for IL-2 in live virus vaccines it may be possible to prevent the severe complications that arise in recipients with an impaired immune system. 相似文献