全文获取类型
收费全文 | 20445篇 |
免费 | 54篇 |
国内免费 | 68篇 |
专业分类
系统科学 | 96篇 |
丛书文集 | 163篇 |
教育与普及 | 31篇 |
理论与方法论 | 73篇 |
现状及发展 | 8078篇 |
研究方法 | 915篇 |
综合类 | 10834篇 |
自然研究 | 377篇 |
出版年
2013年 | 201篇 |
2012年 | 278篇 |
2011年 | 675篇 |
2010年 | 128篇 |
2008年 | 338篇 |
2007年 | 427篇 |
2006年 | 424篇 |
2005年 | 384篇 |
2004年 | 377篇 |
2003年 | 354篇 |
2002年 | 366篇 |
2001年 | 797篇 |
2000年 | 793篇 |
1999年 | 422篇 |
1992年 | 413篇 |
1991年 | 324篇 |
1990年 | 346篇 |
1989年 | 360篇 |
1988年 | 317篇 |
1987年 | 319篇 |
1986年 | 339篇 |
1985年 | 402篇 |
1984年 | 328篇 |
1983年 | 294篇 |
1982年 | 254篇 |
1981年 | 239篇 |
1980年 | 271篇 |
1979年 | 604篇 |
1978年 | 497篇 |
1977年 | 468篇 |
1976年 | 400篇 |
1975年 | 455篇 |
1974年 | 615篇 |
1973年 | 475篇 |
1972年 | 475篇 |
1971年 | 607篇 |
1970年 | 817篇 |
1969年 | 550篇 |
1968年 | 565篇 |
1967年 | 518篇 |
1966年 | 488篇 |
1965年 | 334篇 |
1964年 | 90篇 |
1959年 | 189篇 |
1958年 | 301篇 |
1957年 | 235篇 |
1956年 | 165篇 |
1955年 | 154篇 |
1954年 | 157篇 |
1948年 | 128篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Our understanding of the mode of action of parathyroid hormone-related protein (PTHrP) has changed profoundly during the last decade. Most PTHrP activities are mediated by membrane receptors through autocrine/paracrine pathways. However, both endogenous and exogenous PTHrP also appear to have intracrine effects through translocation into the nucleus. The present review proposes unconventional PTHrP signalling, based on novel clues. First, PTHrP binding to its membrane receptor triggers internalization of the whole complex, mediated by beta-arrestin. There is growing evidence that the receptor and arrestin are the effectors of biological responses, rather than the ligand (or in addition to the ligand). Second, the existence of putative PTHrP targets within the cytoplasm is beginning to be supported. Recent findings of interactions between a COOH-terminus of PTHrP and beta-arrestin and between the PTHrP receptor and 14-3-3 proteins represent the starting point for identification of intracellular partners of both the hormone and its receptor.Received 19 June 2003; received after revision 10 July 2003; accepted 21 July 2003 相似文献
992.
993.
994.
Mignot C Boespflug-Tanguy O Gelot A Dautigny A Pham-Dinh D Rodriguez D 《Cellular and molecular life sciences : CMLS》2004,61(3):369-385
Alexander disease (AXD) is the first primary astrocytic disorder. This encephalopathy is caused by dominant mutations in the glial fibrillary acidic protein (GFAP) gene, encoding the main intermediate filament of astrocyte. Pathologically, this neurodegenerative disease is characterised by dystrophic astrocytes containing intermediate filament aggregates associated with myelin abnormalities.More than 20 GFAP mutations have been reported. Many of them cluster in highly conserved regions between several intermediate filaments. Contrary to other intermediate filament-related diseases, AXD seems to be the consequence of a toxic gain of function induced by aggregates. This is supported by the phenotype of mice overexpressing human GFAP. Nevertheless, GFAP null mice display myelin abnormalities and blood-brain barrier dysfunction that are present in AXD.Given the pivotal role of astrocytes in brain physiology, there are many possibilities for astrocytes to dysfunction and to impair the functions of other cells. Physiopathological hypotheses are discussed in the frame of AXD.Received 11 April 2003; received after revision 22 July 2003; accepted 31 July 2003Both authors contributed equally to this work. 相似文献
995.
Smith NJ Chan HW Osborne JE Thomas WG Hannan RD 《Cellular and molecular life sciences : CMLS》2004,61(21):2695-2703
Activation of the type 1 angiotensin II receptor (AT(1)R) is associated with the aetiology of left ventricular hypertrophy, although the exact intracellular signalling mechanism(s) remain unclear. Transactivation of the epidermal growth factor receptor (EGFR) has emerged as a central mechanism by which the G protein-coupled AT(1)R, which lacks intrinsic tyrosine kinase activity, can stimulate the mitogen-activated protein kinase signalling pathways thought to mediate cardiac hypertrophy. Current studies support a model whereby AT(1)R-dependent transactivation of EGFRs on cardiomyocytes involves stimulation of membrane-bound metalloproteases, which in turn cleave EGFR ligands such as heparin-binding EGF from a plasma membrane-associated precursor. Numerous aspects of the 'triple membrane-passing signalling' paradigm of AT(1)R-induced EGFR transactivation remain to be characterised, including the identity of the specific metalloproteases involved, the intracellular mechanism for their activation and the exact EGFR subtypes required. Here we examine how 'hijacking' of the EGFR might explain the ability of the AT(1)R to elicit the temporally and qualitatively diverse responses characteristic of the hypertrophic phenotype, and discuss the ramifications of delineating these pathways for the development of new therapeutic strategies to combat cardiac hypertrophy. 相似文献
996.
DNA mutations and aberrations are a problem for all forms of life. Eukaryotes specifically have developed ways of identifying and repairing various DNA mutations in a complex and refractory chromatin environment. The chromatin structure is much more than a packaging unit for DNA; it is dynamic. Cells utilize and manipulate chromatin for gene regulation, genome organization and maintenance of genome integrity. Once a DNA aberration has occurred, the various DNA repair machineries interact with chromatin proteins, such as the histone variant H2A.X, and chromatin remodeling machines of the SWI/SNF family to gain access and repair the lesion in a timely manner. Recent studies have thus begun to address the roles of chromatin proteins in DNA repair as well as to dissect the functions of DNA repair machinery in vitro on more physiological, nucleosomal templates. 相似文献
997.
Targeted polymeric micelles for delivery of poorly soluble drugs 总被引:17,自引:0,他引:17
Torchilin VP 《Cellular and molecular life sciences : CMLS》2004,61(19-20):2549-2559
Polymeric micelles (micelles formed by amphiphilic block copolymers) demonstrate a series of attractive properties as drug carriers, such as high stability both in vitro and in vivo and good biocompatibility, and can be successfully used for the solubilization of various poorly soluble pharmaceuticals. These micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. Immunomicelles prepared with cancer-specific monoclonal antibody 2C5 specifically bind to different cancer cells in vitro and demonstrate increased therapeutic activity in vivo. This new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body. 相似文献
998.
Gelsolin superfamily proteins: key regulators of cellular functions 总被引:10,自引:0,他引:10
Silacci P Mazzolai L Gauci C Stergiopulos N Yin HL Hayoz D 《Cellular and molecular life sciences : CMLS》2004,61(19-20):2614-2623
Cytoskeletal rearrangement occurs in a variety of cellular processes and involves a wide spectrum of proteins. Among these, the gelsolin superfamily proteins control actin organization by severing filaments, capping filament ends and nucleating actin assembly [1]. Gelsolin is the founding member of this family, which now contains at least another six members: villin, adseverin, capG, advillin, supervillin and flightless I. In addition to their respective role in actin filament remodeling, these proteins have some specific and apparently non-overlapping particular roles in several cellular processes, including cell motility, control of apoptosis and regulation of phagocytosis (summarized in table 1). Evidence suggests that proteins belonging to the gelsolin superfamily may be involved in other processes, including gene expression regulation. This review will focus on some of the known functions of the gelsolin superfamily proteins, thus providing a basis for reflection on other possible and as yet incompletely understood roles for these proteins. 相似文献
999.
Tsyba L Rynditch AV Boeri E Jabbari K Bernardi G 《Cellular and molecular life sciences : CMLS》2004,61(6):721-726
The localization of HIV-1 proviruses in compositional DNA fractions from 27 AIDS patients during the chronic phase of the disease with depletion of CD4+ and different levels of viremia showed the following. (1) At low viremia, proviruses are predominantly localized in the GC-richest isochores, which are characterized by an open chromatin structure; this result mimics findings on HIV-1 integration in early infected cells in culture. (2) At higher viremia, an increased distribution of proviruses in GC-poor isochores (which match the GC poorness of HIV-1) was found; this suggests a selection of cells in which the isopycnic localization leads to a higher expression of proviruses and, in turn, to higher viremia. (3) At the highest viremia, integrations in GC-rich isochores are often predominant again, but generally not at the same level as in (1); this may be the consequence of new integrations from the extremely abundant RNA copies.Received 21 November 2003; received after revision 13 January 2004: accepted 15 January 2004 相似文献
1000.