全文获取类型
收费全文 | 7253篇 |
免费 | 84篇 |
国内免费 | 101篇 |
专业分类
系统科学 | 131篇 |
丛书文集 | 389篇 |
教育与普及 | 294篇 |
理论与方法论 | 17篇 |
现状及发展 | 673篇 |
研究方法 | 1046篇 |
综合类 | 4883篇 |
自然研究 | 5篇 |
出版年
2019年 | 10篇 |
2018年 | 12篇 |
2017年 | 24篇 |
2016年 | 23篇 |
2015年 | 18篇 |
2014年 | 32篇 |
2013年 | 33篇 |
2012年 | 485篇 |
2011年 | 614篇 |
2010年 | 158篇 |
2009年 | 31篇 |
2008年 | 524篇 |
2007年 | 528篇 |
2006年 | 542篇 |
2005年 | 544篇 |
2004年 | 492篇 |
2003年 | 462篇 |
2002年 | 382篇 |
2001年 | 328篇 |
2000年 | 473篇 |
1999年 | 164篇 |
1998年 | 20篇 |
1997年 | 10篇 |
1996年 | 20篇 |
1994年 | 22篇 |
1993年 | 29篇 |
1992年 | 20篇 |
1991年 | 32篇 |
1990年 | 29篇 |
1989年 | 32篇 |
1988年 | 25篇 |
1987年 | 25篇 |
1986年 | 37篇 |
1985年 | 36篇 |
1984年 | 33篇 |
1983年 | 31篇 |
1982年 | 37篇 |
1981年 | 30篇 |
1980年 | 13篇 |
1979年 | 20篇 |
1971年 | 16篇 |
1970年 | 29篇 |
1966年 | 11篇 |
1959年 | 116篇 |
1958年 | 216篇 |
1957年 | 153篇 |
1956年 | 122篇 |
1955年 | 129篇 |
1954年 | 146篇 |
1948年 | 34篇 |
排序方式: 共有7438条查询结果,搜索用时 250 毫秒
201.
Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus 总被引:1,自引:0,他引:1
Zhu L Vranckx R Khau Van Kien P Lalande A Boisset N Mathieu F Wegman M Glancy L Gasc JM Brunotte F Bruneval P Wolf JE Michel JB Jeunemaitre X 《Nature genetics》2006,38(3):343-349
We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocalization of wild-type and mutant rod proteins in SMC, in conjunction with differences in their coimmunoprecipitation capacities, strongly suggest a dominant-negative effect. Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease. 相似文献
202.
Scorpio A Blank TE Day WA Chabot DJ 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2237-2248
Anthrax has been a major cause of death in grazing animals and an occasional cause of death in humans for thousands of years. Since the late 1800s there has been an exceptional international history of anthrax vaccine development. Due to animal vaccinations, the rate of infection has dropped dramatically. Anthrax vaccines have progressed from uncharacterized whole-cell vaccines in 1881, to pXO2-negative spores in the 1930s, to culture filtrates absorbed to aluminum hydroxide in 1970, and likely to recombinant protective antigen in the near future. Each of these refinements has increased safety without significant loss of efficacy. The threat of genetically engineered, antibiotic and vaccine resistant strains of Bacillus anthracis is fueling hypothesis-driven research and global techniques--including genomics, proteomics and transposon site hybridization--to facilitate the discovery of novel vaccine targets. This review highlights historical achievements and new developments in anthrax vaccine research. 相似文献
203.
Wang X Rochon M Lamprokostopoulou A Lünsdorf H Nimtz M Römling U 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2352-2363
Commensal Escherichia coli form biofilms at body temperature by expressing the extracellular matrix components curli fimbriae and cellulose. The role of curli fimbriae and cellulose in the interaction of commensal E. coli with the intestinal epithelial cell line HT-29 was investigated. Expression of curli fimbriae by the typical commensal isolate E. coli TOB1 caused adherence and internalization of the bacteria and triggered IL-8 production in HT-29 cells. In particular, induction of IL-8 production was complex and involved curli-bound flagellin. While cellulose alone had no effect on the interaction of TOB1 with HT-29 cells, co-expression of cellulose with curli fimbriae decreased adherence to, internalization and IL-8 induction of HT-29 cells. Investigation of a panel of commensal isolates showed a partial correlation between expression of curli fimbriae and enhanced internalization and IL-8 production. In addition, a high immunostimulatory flagellin was identified. Thus, the consequences of expression of extracellular matrix components on commensal bacterial-host interactions are complex. 相似文献
204.
205.
Selenium is an essential trace element. In cattle, selenium deficiency causes dysfunction of various organs, including skeletal
and cardiac muscles. In humans as well, lack of selenium is associated with many disorders, but despite accumulation of clinical
reports, muscle diseases are not generally considered on the list. The goal of this review is to establish the connection
between clinical observations and the most recent advances obtained in selenium biology. Recent results about a possible role
of selenium-containing proteins in muscle formation and repair have been collected. Selenoprotein N is the first selenoprotein
linked to genetic disorders consisting of different forms of congenital muscular dystrophies. Understanding the muscle disorders
associated with selenium deficiency or selenoprotein N dysfunction is an essential step in defining the causes of the disease
and obtaining a better comprehension of the mechanisms involved in muscle formation and maintenance.
Received 13 July 2005; received after revision 9 September 2005; accepted 4 October 2005 相似文献
206.
Gereben B Zeöld A Dentice M Salvatore D Bianco AC 《Cellular and molecular life sciences : CMLS》2008,65(4):570-590
The thyroid hormone plays a fundamental role in the development, growth, and metabolic homeostasis in all vertebrates by affecting
the expression of different sets of genes. A group of thioredoxin fold-containing selenoproteins known as deiodinases control
thyroid hormone action by activating or inactivating the precursor molecule thyroxine that is secreted by the thyroid gland.
These pathways ensure regulation of the availability of the biologically active molecule T3, which occurs in a time-and tissue-specific
fashion. In addition, because cells and plasma are in equilibrium and deiodination affects central thyroid hormone regulation,
these local deiodinase-mediated events can also affect systemic thyroid hormone economy, such as in the case of non-thyroidal
illness. Heightened interest in the field has been generated following the discovery that the deiodinases can be a component
in both the Sonic hedgehog signaling pathway and the TGR-5 signaling cascade, a G-protein-coupled receptor for bile acids.
These new mechanisms involved in deiodinase regulation indicate that local thyroid hormone activation and inactivation play
a much broader role than previously thought.
Received 29 August 2007; received after revision 11 October 2007; accepted 16 October 2007 相似文献
207.
208.
Oddi S Fezza F Pasquariello N De Simone C Rapino C Dainese E Finazzi-Agrò A Maccarrone M 《Cellular and molecular life sciences : CMLS》2008,65(5):840-850
Anandamide is a lipid messenger that carries out a wide variety of biological functions. It has been suggested that anandamide
accumulation involves binding to a saturable cellular component. To identify the structure(s) involved in this process, we
analyzed the intracellular distribution of both biotinylated and radiolabeled anandamide, providing direct evidence that lipid
droplets, also known as adiposomes, constitute a dynamic reservoir for the sequestration of anandamide. In addition, confocal
microscopy and biochemical studies revealed that the anandamide-hydrolase is also spatially associated with lipid droplets,
and that cells with a larger adiposome compartment have an enhanced catabolism of anandamide. Overall, these findings suggest
that adiposomes may have a critical role in accumulating anandamide, possibly by connecting plasma membrane to internal organelles
along the metabolic route of this endocannabinoid.
S. Oddi, F. Fezza: These authors contributed equally to the study. 相似文献
209.
Molecular and Cellular Basis of Regeneration and Tissue Repair 总被引:3,自引:0,他引:3
Rossi L Salvetti A Batistoni R Deri P Gremigni V 《Cellular and molecular life sciences : CMLS》2008,65(1):16-23
Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues. 相似文献
210.
Src-family kinases (SFKs) regulate different granulocyte and monocyte/macrophage responses. Accumulating evidence suggests that members of this family are implicated in signal transduction pathways regulating phagocytic cell migration and recruitment into inflammatory sites. Macrophages with a genetic deficiency of SFKs display marked alterations in cytoskeleton dynamics, polarization and migration. This same phenotype is found in cells with either a lack of SFK substrates and/or interacting proteins such as Pyk2/FAK, c-Cbl and p190RhoGAP. Notably, SFKs and their downstream targets also regulate monocyte recruitment into inflammatory sites. Depending on the type of assay used, neutrophil migration in vitro may be either dependent on or independent of SFKs. Also neutrophil recruitment in in vivo models of inflammation may be regulated differently by SFKs depending on the tissue involved. In this review we will discuss possible mechanisms by which SFKs may regulate phagocytic cell migratory abilities. 相似文献