全文获取类型
收费全文 | 17227篇 |
免费 | 42篇 |
国内免费 | 53篇 |
专业分类
系统科学 | 253篇 |
丛书文集 | 444篇 |
教育与普及 | 36篇 |
理论与方法论 | 50篇 |
现状及发展 | 7948篇 |
研究方法 | 724篇 |
综合类 | 7719篇 |
自然研究 | 148篇 |
出版年
2012年 | 203篇 |
2011年 | 408篇 |
2010年 | 97篇 |
2009年 | 94篇 |
2008年 | 271篇 |
2007年 | 344篇 |
2006年 | 290篇 |
2005年 | 298篇 |
2004年 | 271篇 |
2003年 | 325篇 |
2002年 | 260篇 |
2001年 | 609篇 |
2000年 | 609篇 |
1999年 | 344篇 |
1992年 | 328篇 |
1991年 | 253篇 |
1990年 | 298篇 |
1989年 | 271篇 |
1988年 | 262篇 |
1987年 | 276篇 |
1986年 | 284篇 |
1985年 | 338篇 |
1984年 | 242篇 |
1983年 | 219篇 |
1982年 | 200篇 |
1981年 | 238篇 |
1980年 | 261篇 |
1979年 | 568篇 |
1978年 | 463篇 |
1977年 | 469篇 |
1976年 | 351篇 |
1975年 | 374篇 |
1974年 | 583篇 |
1973年 | 455篇 |
1972年 | 413篇 |
1971年 | 510篇 |
1970年 | 656篇 |
1969年 | 573篇 |
1968年 | 492篇 |
1967年 | 528篇 |
1966年 | 439篇 |
1965年 | 330篇 |
1964年 | 86篇 |
1959年 | 198篇 |
1958年 | 293篇 |
1957年 | 192篇 |
1956年 | 172篇 |
1955年 | 167篇 |
1954年 | 159篇 |
1948年 | 87篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
781.
Hoekstra PJ Anderson GM Limburg PC Korf J Kallenberg CG Minderaa RB 《Cellular and molecular life sciences : CMLS》2004,61(7-8):886-898
Tourettes syndrome is a childhood-onset neuropsychiatric disorder characterized by the presence of both multiple motor and vocal tics. While the pathogenesis at a molecular and cellular level remains unknown, structural and functional neuroimaging studies point to the involvement of the basal ganglia and related cortico-striato-thalamo-cortical circuits as the neuroanatomical site for Tourettes syndrome. Moreover, Tourettes syndrome has a strong genetic component, and considerable progress has been made in understanding the mode of transmission and in identifying potential genomic loci. Summaries of recent findings in these areas will be reviewed, followed by a critical overview of findings both supporting and challenging the proposed autoimmune hypothesis of Tourettes syndrome. We conclude that Tourettes syndrome is a heterogeneous disorder, and that immune factors may indeed be involved in some patients.Received 12 August 2003; received after revision 8 October 2003; accepted 31 October 2003 相似文献
782.
Profiling of the secreted proteins during 3T3-L1 adipocyte differentiation leads to the identification of novel adipokines 总被引:3,自引:0,他引:3
Wang P Mariman E Keijer J Bouwman F Noben JP Robben J Renes J 《Cellular and molecular life sciences : CMLS》2004,61(18):2405-2417
Adipose tissue is an endocrine organ capable of secreting a number of adipokines with a role in the regulation of
adipose tissue and whole-body metabolism. We used two-dimensional gel electrophoresis combined with mass spectrometry to
profile the secreted proteins from (pre)adipocytes. The culture medium of 3T3-L1 cells during adipocyte differentiation
was screened, and 41 proteins that responded to blocking of secretion by 20°C treatment and/or brefeldin A treatment
were identified. Prohibitin, stress-70 protein, and adhesion-regulating molecule 1 are reported for the first time as
secreted proteins. In addition, procollagen C-proteinase enhancer protein, galectin-1, cyclophilin A and C, and SF20/IL-25
are newly identified as adipocyte secreted factors. Secretion profiles indicated a dynamic environment including an
actively remodeling extracellular matrix and several factors involved in growth regulation.Received 15 June 2004; received after revision 26 July 2004; accepted 2 August 2004 相似文献
783.
Panizzi P Friedrich R Fuentes-Prior P Bode W Bock PE 《Cellular and molecular life sciences : CMLS》2004,61(22):2793-2798
Staphylocoagulase (SC) secreted by Staphylococcus aureus is a potent non-proteolytic activator of the blood coagulation zymogen prothrombin and the prototype of a newly established
zymogen
activator and
adhesion
protein (ZAAP) family. The conformationally activated SC·prothrombin complex specifically cleaves fibrinogen to fibrin, which propagates the growth of bacteria-fibrin-platelet vegetations in acute bacterial endocarditis. Our recent 2.2 Å X-ray crystal structures of an active SC fragment [SC(1-325)] bound to the prothrombin zymogen catalytic domain, prethrombin 2, demonstrated that SC(1-325) represents a new type of non-proteolytic activator with a unique fold. The observed insertion of the SC(1-325) N-terminus into the Ile 16 cleft of prethrombin 2, which triggers the activating conformational change, provided the first unambiguous structural evidence for the molecular sexuality mechanism of non-proteolytic zymogen activation. Based on the SC(1-325) fold, a new family of bifunctional zymogen activator and adhesion proteins was identified that possess N-terminal domains homologous to SC(1-325) and C-terminal domains that mediate adhesion to plasma or extracellular matrix proteins. Further investigation of the ZAAP family may lead to new insights into the mechanisms of bacterial factors that hijack zymogens of the human blood coagulation and fibrinolytic systems to promote and disseminate endocarditis and other infectious diseases.Received 30 June 2004; received after revision 28 July 2004; accepted 4 August 2004 相似文献
784.
785.
The myelin proteolipid protein (PLP) gene (Plp) encodes the most abundant protein found in myelin from the central nervous system (CNS). Expression of the gene is regulated in a spatiotemporal manner with maximal levels of expression occurring in oligodendrocytes during the active myelination period of CNS development, although other cell types in the CNS as well as in the periphery can express the gene to a much lower degree. In oligodendrocytes, Plp gene expression is tightly regulated. Underexpression or overexpression of the gene has been shown to have adverse effects in humans and other vertebrates. In light of this strict control, this review provides an overview of the current knowledge of Plp gene regulation.Received 4 August 2003; received after revision 17 September 2003; accepted 24 September 2003 相似文献
786.
DNA damage repair and transcription 总被引:2,自引:0,他引:2
787.
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
788.
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
789.
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
790.
Oncogenic protein tyrosine kinases 总被引:8,自引:0,他引:8
Ménard S Casalini P Campiglio M Pupa SM Tagliabue E 《Cellular and molecular life sciences : CMLS》2004,61(23):2965-2978
HER2 (human epidermal growth factor receptor-2; also known as erbB2) and its relatives HER1 (epidermal growth factor receptor; EGFR), HER3 and HER4 belong to the HER family of receptor tyrosine kinases. In normal cells, activation of this receptor tyrosine kinase family triggers a rich network of signaling pathways that control normal cell growth, differentiation, motility and adhesion in several cell lineages. The first tumor studied for an alteration of the HER2 oncogene is breast carcinoma, and so far the majority of studies have been performed on this oncotype. Although involvement of HER2 as a cause of human cell transformation needs to be further investigated, overexpression of the HER2 oncogene in human breast carcinomas has been associated with a more aggressive course of disease. It has been suggested that this association depends on HER2-driven proliferation, vessel formation and/or invasiveness; however, poor prognosis may not be directly related to the presence of the oncoprotein on the cell membrane but instead to the breast carcinoma subset identified by HER2 overexpression and characterized by a peculiar gene expression profile, as recently identified. HER2-positive tumors were recently shown to benefit from anthracyclin treatment and to be resistant to endocrine therapy. Despite the fact that many pathways interacting with HER2 are still not fully understood, this tyrosine kinase receptor is, to date, a promising molecule for targeted therapy. 相似文献