全文获取类型
收费全文 | 1632篇 |
免费 | 20篇 |
国内免费 | 24篇 |
专业分类
系统科学 | 25篇 |
丛书文集 | 16篇 |
教育与普及 | 86篇 |
理论与方法论 | 9篇 |
现状及发展 | 162篇 |
研究方法 | 302篇 |
综合类 | 1075篇 |
自然研究 | 1篇 |
出版年
2022年 | 5篇 |
2021年 | 3篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 10篇 |
2016年 | 5篇 |
2015年 | 3篇 |
2013年 | 5篇 |
2012年 | 134篇 |
2011年 | 155篇 |
2010年 | 40篇 |
2009年 | 5篇 |
2008年 | 123篇 |
2007年 | 149篇 |
2006年 | 148篇 |
2005年 | 135篇 |
2004年 | 120篇 |
2003年 | 82篇 |
2002年 | 89篇 |
2001年 | 65篇 |
2000年 | 76篇 |
1999年 | 27篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 16篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1971年 | 3篇 |
1970年 | 7篇 |
1966年 | 6篇 |
1959年 | 15篇 |
1958年 | 29篇 |
1957年 | 18篇 |
1956年 | 20篇 |
1955年 | 17篇 |
1954年 | 23篇 |
1948年 | 10篇 |
1934年 | 2篇 |
排序方式: 共有1676条查询结果,搜索用时 31 毫秒
991.
992.
993.
Qiu W Hu M Sridhar A Opeskin K Fox S Shipitsin M Trivett M Thompson ER Ramakrishna M Gorringe KL Polyak K Haviv I Campbell IG 《Nature genetics》2008,40(5):650-655
There is increasing evidence showing that the stromal cells surrounding cancer epithelial cells, rather than being passive bystanders, might have a role in modifying tumor outgrowth. The molecular basis of this aspect of carcinoma etiology is controversial. Some studies have reported a high frequency of genetic aberrations in carcinoma-associated fibroblasts (CAFs), whereas other studies have reported very low or zero mutation rates. Resolution of this contentious area is of critical importance in terms of understanding both the basic biology of cancer as well as the potential clinical implications of CAF somatic alterations. We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis of CAFs derived from breast and ovarian carcinomas using a 500K SNP array platform. Our data show conclusively that LOH and copy number alterations are extremely rare in CAFs and cannot be the basis of the carcinoma-promoting phenotypes of breast and ovarian CAFs. 相似文献
994.
995.
Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis 总被引:12,自引:0,他引:12
Lundmark F Duvefelt K Iacobaeus E Kockum I Wallström E Khademi M Oturai A Ryder LP Saarela J Harbo HF Celius EG Salter H Olsson T Hillert J 《Nature genetics》2007,39(9):1108-1113
Multiple sclerosis is a chronic, often disabling, disease of the central nervous system affecting more than 1 in 1,000 people in most western countries. The inflammatory lesions typical of multiple sclerosis show autoimmune features and depend partly on genetic factors. Of these genetic factors, only the HLA gene complex has been repeatedly confirmed to be associated with multiple sclerosis, despite considerable efforts. Polymorphisms in a number of non-HLA genes have been reported to be associated with multiple sclerosis, but so far confirmation has been difficult. Here, we report compelling evidence that polymorphisms in IL7R, which encodes the interleukin 7 receptor alpha chain (IL7Ralpha), indeed contribute to the non-HLA genetic risk in multiple sclerosis, demonstrating a role for this pathway in the pathophysiology of this disease. In addition, we report altered expression of the genes encoding IL7Ralpha and its ligand, IL7, in the cerebrospinal fluid compartment of individuals with multiple sclerosis. 相似文献
996.
Roglio I Bianchi R Giatti S Cavaletti G Caruso D Scurati S Crippa D Garcia-Segura LM Camozzi F Lauria G Melcangi RC 《Cellular and molecular life sciences : CMLS》2007,64(9):1158-1168
In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5αandrostan-3α, 17β-diol (3α-diol)
therapies on diabetic neuropathy. Diabetes was induced in adult male rats by the injection of streptozotocin and resulted
in decreased T and increased 3α-diol levels in plasma and in decreased levels of pregnenolone and DHT in the sciatic nerve.
Moreover, a reduced expression of the enzyme converting Tinto DHT (i.e., the 5α-reductase) also occurs at the level of sciatic nerve, suggesting that the decrease of DHT levels could be due to
an impairment of this enzyme. Chronic treatment for 1 month with DHT or 3α-diol increased tail nerve conduction velocity and
partially counteracted the increase of thermal threshold induced by diabetes. Treatment with DHT increased tibial Na+,K+-ATPase activity and the expression of myelin protein P0 in the sciatic nerve.DHT, 3α-diol and T reversed the reduction of
intra-epidermal nerve fiber density induced by diabetes. These observations indicate that T metabolites can reverse behavioral,
neurophysiological, morphological and biochemical alterations induced by peripheral diabetic neuropathy.
I. Roglio, R. Bianchi: These authors contributed equally to this study.
Received 4 January 2007; received after revision 13 February 2007; accepted 27 March 2007 相似文献
997.
Ramírez CL Cadiñanos J Varela I Freije JM López-Otín C 《Cellular and molecular life sciences : CMLS》2007,64(2):155-170
Disorders in which individuals exhibit certain features of aging early in life are referred to as segmental progeroid syndromes.
With the progress that has been made in understanding the etiologies of these conditions in the past decade, potential therapeutic
options have begun to move from the realm of improbability to initial stages of testing. Among these syndromes, relevant advances
have recently been made in Werner syndrome, one of several progeroid syndromes characterized by defective DNA helicases, and
Hutchinson-Gilford progeria syndrome, which is characterized by aberrant processing of the nuclear envelope protein lamin
A. Although best known for their causative roles in these illnesses, Werner protein and lamin A have also recently emerged
as key players vulnerable to epigenetic changes that contribute to tumorigenesis and aging. These advances further demonstrate
that understanding progeroid syndromes and introducing adequate treatments will not only prove beneficial to patients suffering
from these dramatic diseases, but will also provide new mechanistic insights into cancer and normal aging processes.
Received 28 July 2006; received after revision 5 September 2006; accepted 13 October 2006 相似文献
998.
Calorie restriction and the nutrient sensing signaling pathways 总被引:3,自引:0,他引:3
Calorie restriction (CR) is the most potent regimen known to extend the life span in multiple species. CR has also been shown
to ameliorate several age-associated disorders in mammals and perhaps humans. CR induces diverse metabolic changes in organisms,
and it is currently unclear whether and how these metabolic changes lead to life span extension. Recent studies in model systems
have provided insight into the molecular mechanisms by which CR extends life span. In this review, we summarize and provide
recent updates on multiple nutrient signaling pathways that have been connected to CR and longevity regulation. The roles
of highly conserved longevity regulators – the Sirtuin family – in CR are also discussed.
Received 25 August 2006; received after revision 9 October 2006; accepted 13 December 2006 相似文献
999.
Tartaglia M Pennacchio LA Zhao C Yadav KK Fodale V Sarkozy A Pandit B Oishi K Martinelli S Schackwitz W Ustaszewska A Martin J Bristow J Carta C Lepri F Neri C Vasta I Gibson K Curry CJ Siguero JP Digilio MC Zampino G Dallapiccola B Bar-Sagi D Gelb BD 《Nature genetics》2007,39(1):75-79
Noonan syndrome is a developmental disorder characterized by short stature, facial dysmorphia, congenital heart defects and skeletal anomalies. Increased RAS-mitogen-activated protein kinase (MAPK) signaling due to PTPN11 and KRAS mutations causes 50% of cases of Noonan syndrome. Here, we report that 22 of 129 individuals with Noonan syndrome without PTPN11 or KRAS mutation have missense mutations in SOS1, which encodes a RAS-specific guanine nucleotide exchange factor. SOS1 mutations cluster at codons encoding residues implicated in the maintenance of SOS1 in its autoinhibited form. In addition, ectopic expression of two Noonan syndrome-associated mutants induces enhanced RAS and ERK activation. The phenotype associated with SOS1 defects lies within the Noonan syndrome spectrum but is distinctive, with a high prevalence of ectodermal abnormalities but generally normal development and linear growth. Our findings implicate gain-of-function mutations in a RAS guanine nucleotide exchange factor in disease for the first time and define a new mechanism by which upregulation of the RAS pathway can profoundly change human development. 相似文献
1000.
Lipid droplets have been considered for a long time as inert intracytoplasmic deposits formed within cells under various conditions. Recently, new tools and new approaches have been used to visualize and study these intracellular structures. This revealed new aspects of lipid droplets biology and pointed out their organized structure and dynamic composition. In adipocytes, the specialized cell type for the storage of energy as fat, lipid droplets are particularly well-developed organelles and exhibit unique properties. Also discussed in this paper is the view that lipid droplets, through specific candidate constituents, can play a role in sensing the level of their lipid stores by adipocytes. 相似文献