全文获取类型
收费全文 | 620篇 |
免费 | 49篇 |
国内免费 | 2篇 |
出版年
2023年 | 5篇 |
2022年 | 5篇 |
2021年 | 19篇 |
2020年 | 15篇 |
2019年 | 12篇 |
2018年 | 27篇 |
2017年 | 15篇 |
2016年 | 14篇 |
2015年 | 42篇 |
2014年 | 33篇 |
2013年 | 44篇 |
2012年 | 57篇 |
2011年 | 47篇 |
2010年 | 21篇 |
2009年 | 23篇 |
2008年 | 21篇 |
2007年 | 33篇 |
2006年 | 21篇 |
2005年 | 20篇 |
2004年 | 24篇 |
2003年 | 30篇 |
2002年 | 14篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 14篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1991年 | 7篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1977年 | 9篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1965年 | 2篇 |
1962年 | 2篇 |
1960年 | 2篇 |
排序方式: 共有671条查询结果,搜索用时 15 毫秒
81.
Summary A study of mitosis and meiosis in Schizosaccharomyces pombe Lindner has been carried out with the Giemsa procedure.The pattern of mitosis in the vegetative cells of S. pombe does not differ in its main features from that of other fungi, in that it appears to be accomplished without the help of a spindle apparatus and without formation of typical metaphase plates. However, there is good evidence for the presence of centrosomes which may exert some pulling effect at the ana-telophase stages.Meiosis in the ascogenous cells is characterized by a leptotene, bar-like stage followed by a tetrad formation revealing at least 3 bivalents.
Travail achevé à l'Institut de Botanique générale de l'Université de Genève, en hommage posthume au Prof. W. H. Schopfer. 相似文献
Travail achevé à l'Institut de Botanique générale de l'Université de Genève, en hommage posthume au Prof. W. H. Schopfer. 相似文献
82.
83.
84.
Chong YP Mulhern TD Zhu HJ Fujita DJ Bjorge JD Tantiongco JP Sotirellis N Lio DS Scholz G Cheng HC 《The Journal of biological chemistry》2004,279(20):20752-20766
Although C-terminal Src kinase (CSK)-homologous kinase (CHK) is generally believed to inactivate Src-family tyrosine kinases (SFKs) by phosphorylating their consensus C-terminal regulatory tyrosine (Tyr(T)), exactly how CHK inactivates SFKs is not fully understood. Herein, we report that in addition to phosphorylating Tyr(T), CHK can inhibit SFKs by a novel non-catalytic mechanism. First, CHK directly binds to the SFK members Hck, Lyn, and Src to form stable protein complexes. The complex formation is mediated by a non-catalytic Tyr(T)-independent mechanism because it occurs even in the absence of ATP or when Tyr(T) of Hck is replaced by phenylalanine. Second, the non-catalytic CHK-SFK interaction alone is sufficient to inactivate SFKs by inhibiting the catalytic activity of autophosphorylated SFKs. Third, CHK and Src co-localize to specific plasma membrane microdomains of rat brain cells, suggesting that CHK is in close proximity to Src such that it can effectively inactivate Src in vivo. Fourth, native CHK.Src complex exists in rat brain, and recombinant CHK.Hck complex exists in transfected HEK293T cells, implying that CHK forms stable complexes with SFKs in vivo. Taken together, our findings suggest that CHK inactivates SFKs (i) by phosphorylating their Tyr(T) and (ii) by this novel Tyr(T)-independent mechanism involving direct binding of CHK to SFKs. It has been documented that autophosphorylated SFKs can still be active, in some cases even when their Tyr(T) is phosphorylated. Thus, the ability of the Tyr(T)-independent mechanism to suppress the activity of both non-phosphorylated and autophosphorylated SFKs represents a fail-safe measure employed by CHK to down-regulate SFK signaling under all circumstances. 相似文献
85.
86.
87.
Heirman I Ginneberge D Brigelius-Flohé R Hendrickx N Agostinis P Brouckaert P Rottiers P Grooten J 《Free radical biology & medicine》2006,40(2):285-294
Using tumor cell-restricted overexpression of glutathione peroxidase 4 (GP x 4), we investigated the contribution of tumor cell eicosanoids to solid tumor growth and malignant progression in two tumor models differing in tumorigenic potential. By lowering cellular lipid hydroperoxide levels, GP x 4 inhibits cyclooxygenase (COX) and lipoxygenase (LOX) activities. GP x 4 overexpression drastically impeded solid tumor growth of weakly tumorigenic L929 fibrosarcoma cells, whereas B16BL6 melanoma solid tumor growth was unaffected. Yet, GP x 4 overexpression did markedly increase the sensitivity of B16BL6 tumors to angio-destructive TNF-alpha therapy and abolished the metastatic lung colonizing capacity of B16BL6 cells. Furthermore, the GP x 4-mediated suppression of tumor cell prostaglandin E(2) (PGE(2)) production impeded the induction of COX-2 expression by the tumor stress conditions hypoxia and inflammation. Thus, our results reflect a PGE(2)-driven positive feedback loop for COX-2 expression in tumor cells. This was further supported by the restoration of COX-2 induction capacity of GP x 4-overexpressing L929 tumor cells when cultured in the presence of exogenous PGE(2). Thus, although COX-2 expression and eicosanoid production may be enabled by PGE(2) from the tumor microenvironment, our results demonstrate the predominant tumor cell origin of protumoral eicosanoids, promoting solid tumor growth of weakly tumorigenic tumors and malignant progression of strongly tumorigenic tumors. 相似文献
88.
Vermeulen W Van Troys M Bourry D Dewitte D Rossenu S Goethals M Borremans FA Vandekerckhove J Martins JC Ampe C 《Journal of molecular biology》2006,359(5):1277-1292
The HeadPiece (HP) domain, present in several F-actin-binding multi-domain proteins, features a well-conserved, solvent-exposed PXWK motif in its C-terminal subdomain. The latter is an autonomously folding subunit comprised of three alpha-helices organised around a hydrophobic core, with the sequence motif preceding the last helix. We report the contributions of each conserved residue in the PXWK motif to human villin HP function and structure, as well as the structural implications of the naturally occurring Pro to Ala mutation in dematin HP. NMR shift perturbation mapping reveals that substitution of each residue by Ala induces only minor, local perturbations in the full villin HP structure. CD spectroscopic thermal analysis, however, shows that the Pro and Trp residues in the PXWK motif afford stabilising interactions. This indicates that, in addition to the residues in the hydrophobic core, the Trp-Pro stacking within the motif contributes to HP stability. This is reinforced by our data on isolated C-terminal HP subdomains where the Pro is also essential for structure formation, since the villin, but not the dematin, C-terminal subdomain is structured. Proper folding can be induced in the dematin C-terminal subdomain by exchanging the Ala for Pro. Conversely, the reverse substitution in the villin C-terminal subdomain leads to loss of structure. Thus, we demonstrate a crucial role for this proline residue in structural stability and folding potential of HP (sub)domains consistent with Pro-Trp stacking as a more general determinant of protein stability. 相似文献
89.
Daisy H. Dent Robert Bagchi David Robinson Noreen Majalap-Lee David F. R. P. Burslem 《Plant and Soil》2006,288(1-2):197-215
The extent to which plant communities are determined by resource availability is a central theme in ecosystem science, but patterns of small-scale variation in resource availability are poorly known. Studies of carbon (C) and nutrient cycling provide insights into factors limiting tree growth and forest productivity. To investigate rates of tropical forest litter production and decomposition in relation to nutrient availability and topography in the absence of confounding large-scale variation in climate and altitude we quantified nutrient fluxes via litterfall and leaf litter decomposition within three distinct floristic associations of tropical rain forest growing along a soil fertility gradient at the Sepilok Forest Reserve (SFR), Sabah, Malaysia. The quantity and nutrient content of small litter decreased along a gradient of soil nutrient availability from alluvial forest (most fertile) through sandstone forest to heath forest (least fertile). Temporal variation in litterfall was greatest in the sandstone forest, where the amount of litter was correlated negatively with rainfall in the previous month. Mass loss and N and P release were fastest from alluvial forest litter, and slowest from heath forest litter. All litter types decomposed most rapidly in the alluvial forest. Stand-level N and P use efficiencies (ratios of litter dry mass to nutrient content) were greatest for the heath forest followed by the sandstone ridge, sandstone valley and alluvial forests, respectively. We conclude that nutrient supply limits productivity most in the heath forest and least in the alluvial forest. Nutrient supply limited productivity in sandstone forest, especially on ridge and hill top sites where nutrient limitation may be exacerbated by reduced rates of litter decomposition during dry periods. The fluxes of N and P varied significantly between the different floristic communities at SFR and these differences may contribute to small-scale variation in species composition. 相似文献
90.
Laura A.E. HughesCarolina A.J. Khalid-de Bakker Kim M. SmitsPiet A. van den Brandt Daisy JonkersNita Ahuja James G. HermanMatty P. Weijenberg Manon van Engeland 《生物化学与生物物理学报:癌评论》2012,1825(1):77-85
In recent years, attention has focused on the biology and potential clinical importance of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). While it is generally well accepted that etiologically and clinically distinct subgroups exist in this disease, a precise definition of CIMP remains to be established. Here, we summarize existing literature that documents the prevalence of CIMP in CRC, with particular attention to the various methods and definitions used to classify a tumor as CIMP positive. Through a systematic review on both case-series and population based studies, we examined only original research articles reporting on sporadic CRC and/or adenomas in unselected cases. Forty-eight papers published between January 1999 and August 2011 met the inclusion criteria. We describe the use of multiple gene panels, marker threshold values, and laboratory techniques which results in a wide range in the prevalence of CIMP. Because there is no universal standard or consensus on quantifying the phenotype, establishing its true prevalence is a challenge. This bottleneck is becoming increasingly evident as molecular pathological epidemiology continues to offer possibilities for clear answers regarding environmental risk factors and disease trends. For the first time, large, unselected series of cases are available for analysis, but comparing populations and pooling data will remain a challenge unless a universal definition of CIMP and a consensus on analysis can be reached, and the primary cause of CIMP identified. 相似文献