全文获取类型
收费全文 | 2905篇 |
免费 | 238篇 |
专业分类
3143篇 |
出版年
2023年 | 7篇 |
2022年 | 24篇 |
2021年 | 48篇 |
2020年 | 30篇 |
2019年 | 43篇 |
2018年 | 50篇 |
2017年 | 54篇 |
2016年 | 67篇 |
2015年 | 112篇 |
2014年 | 139篇 |
2013年 | 160篇 |
2012年 | 194篇 |
2011年 | 224篇 |
2010年 | 123篇 |
2009年 | 151篇 |
2008年 | 169篇 |
2007年 | 201篇 |
2006年 | 171篇 |
2005年 | 179篇 |
2004年 | 164篇 |
2003年 | 160篇 |
2002年 | 151篇 |
2001年 | 40篇 |
2000年 | 23篇 |
1999年 | 30篇 |
1998年 | 44篇 |
1997年 | 31篇 |
1996年 | 23篇 |
1995年 | 41篇 |
1994年 | 27篇 |
1993年 | 32篇 |
1992年 | 18篇 |
1991年 | 24篇 |
1990年 | 27篇 |
1989年 | 21篇 |
1988年 | 20篇 |
1987年 | 9篇 |
1986年 | 12篇 |
1985年 | 7篇 |
1984年 | 11篇 |
1982年 | 12篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 7篇 |
1975年 | 4篇 |
1971年 | 4篇 |
1970年 | 7篇 |
1968年 | 3篇 |
排序方式: 共有3143条查询结果,搜索用时 0 毫秒
41.
Elke Ueberham Ricco Lindner Manja Kamprad Rico Hiemann Nadja Hilger Barbara Woithe Doris Mahn Michael Cross Ulrich Sack Rolf Gebhardt Thomas Arendt Uwe Ueberham 《Journal of cellular and molecular medicine》2008,12(2):622-638
Terminal differentiation requires molecules also involved in aging such as the cell cycle inhibitor p16(INK4a).Like other organs, the adult liver represents a quiescent organ with terminal differentiated cells, hepatocytes and cholangiocytes. These cells retain the ability to proliferate in response to liver injury or reduction of liver mass. However, under conditions which prevent mitotic activation of hepatocytes, regeneration can occur instead from facultative hepatic stem cells.For therapeutic application a non-toxic activation of this stem cell compartment is required. We have established transgenic mice with conditional overexpression of the cell cycle inhibitor p16(INK4a) in hepatocytes and have provoked and examined oval cell activation in adult liver in response to a range of proliferative stimuli.We could show that the liver specific expression of p16(INK4a) leads to a faster differentiation of hepatocytes and an activation of oval cells already in postnatal mice without negative consequences on liver function. 相似文献
42.
The EGF-CFC factor Oep/Cripto1/Frl1 has been implicated in embryogenesis and several human cancers. During vertebrate development, Oep/Cripto1/Frl1 has been shown to act as an essential coreceptor in the TGFbeta/Nodal pathway, which is crucial for germ layer formation. Although studies in cell cultures suggest that Oep/Cripto1/Frl1 is also implicated in other pathways, in vivo it is solely regarded as a Nodal coreceptor. We have found that Rasl11b, a small GTPase belonging to a Ras subfamily of putative tumor suppressor genes, modulates Oep function in zebrafish independently of the Nodal pathway. rasl11b down regulation partially rescues endodermal and prechordal plate defects of zygotic oep(-/-) mutants (Zoep). Rasl11b inhibitory action was only observed in oep-deficient backgrounds, suggesting that normal oep expression prevents Rasl11b function. Surprisingly, rasl11b down regulation does not rescue mesendodermal defects in other Nodal pathway mutants, nor does it influence the phosphorylation state of the downstream effector Smad2. Thus, Rasl11b modifies the effect of Oep on mesendoderm development independently of the main known Oep output: the Nodal signaling pathway. This data suggests a new branch of Oep signaling that has implications for germ layer development, as well as for studies of Oep/Frl1/Cripto1 dysfunction, such as that found in tumors. 相似文献
43.
44.
Induced disease resistance of plants is often associated with an enhanced capacity to activate cellular defense responses to pathogen attack, named the "primed" state of the plant. Exopolysaccharides of Pantoea agglomerans have recently been reported as the first priming active component of bacterial origin in wheat cells. We now show that Pantoea exopolysaccharides also prime rice cells for better elicitation of a rapid oxidative burst. In contrast, in tobacco and parsley cell cultures Pantoea exopolysaccharides activate the oxidative burst response directly. Our results point to a different recognition and/or mode of action of Pantoea exopolysaccharides in monocot and dicot plants. 相似文献
45.
Nuccitelli R Pliquett U Chen X Ford W James Swanson R Beebe SJ Kolb JF Schoenbach KH 《Biochemical and biophysical research communications》2006,343(2):351-360
We have discovered a new, drug-free therapy for treating solid skin tumors. Pulsed electric fields greater than 20 kV/cm with rise times of 30 ns and durations of 300 ns penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. Melanomas shrink by 90% within two weeks following a cumulative field exposure time of 120 micros. A second treatment at this time can result in complete remission. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin. Each pulse deposits 0.2 J and 100 pulses increase the temperature of the treated region by only 3 degrees C, ten degrees lower than the minimum temperature for hyperthermia effects. 相似文献
46.
William D Teale Taras Pasternak Cristina Dal Bosco Alexander Dovzhenko Krystyna Kratzat Wolfgang Bildl Manuel Schwrer Thorsten Falk Benadetto Ruperti Jonas V Schaefer Mojgan Shahriari Lena Pilgermayer Xugang Li Florian Lübben Andreas Plückthun Uwe Schulte Klaus Palme 《The EMBO journal》2021,40(1)
The transport of auxin controls the rate, direction and localization of plant growth and development. The course of auxin transport is defined by the polar subcellular localization of the PIN proteins, a family of auxin efflux transporters. However, little is known about the composition and regulation of the PIN protein complex. Here, using blue‐native PAGE and quantitative mass spectrometry, we identify native PIN core transport units as homo‐ and heteromers assembled from PIN1, PIN2, PIN3, PIN4 and PIN7 subunits only. Furthermore, we show that endogenous flavonols stabilize PIN dimers to regulate auxin efflux in the same way as does the auxin transport inhibitor 1‐naphthylphthalamic acid (NPA). This inhibitory mechanism is counteracted both by the natural auxin indole‐3‐acetic acid and by phosphomimetic amino acids introduced into the PIN1 cytoplasmic domain. Our results lend mechanistic insights into an endogenous control mechanism which regulates PIN function and opens the way for a deeper understanding of the protein environment and regulation of the polar auxin transport complex. 相似文献
47.
Maximilian Schmid Bianca Dufner Julius Dürk Konstanze Bedal Kristina Stricker Lukas Ali Prokoph Christoph Koch Anja K. Wege Henner Zirpel Ger van Zandbergen Rupert Ecker Bogdan Boghiu Uwe Ritter 《PloS one》2015,10(10)
Characterization of host-pathogen interactions is a fundamental approach in microbiological and immunological oriented disciplines. It is commonly accepted that host cells start to change their phenotype after engulfing pathogens. Techniques such as real time PCR or ELISA were used to characterize the genes encoding proteins that are associated either with pathogen elimination or immune escape mechanisms. Most of such studies were performed in vitro using primary host cells or cell lines. Consequently, the data generated with such approaches reflect the global RNA expression or protein amount recovered from all cells in culture. This is justified when all host cells harbor an equal amount of pathogens under experimental conditions. However, the uptake of pathogens by phagocytic cells is not synchronized. Consequently, there are host cells incorporating different amounts of pathogens that might result in distinct pathogen-induced protein biosynthesis. Therefore, we established a technique able to detect and quantify the number of pathogens in the corresponding host cells using immunofluorescence-based high throughput analysis. Paired with multicolor staining of molecules of interest it is now possible to analyze the infection profile of host cell populations and the corresponding phenotype of the host cells as a result of parasite load. 相似文献
48.
Marcia L. Moss Garrit Koller Jörg W. Bartsch Sinja Rakow Uwe Schlomann Fred H. Rasmussen 《Analytical biochemistry》2015
We have developed a new amplification system for proteinases that is sensitive, simple, and inexpensive to run, exemplified by a horseradish peroxidase (HRP)-conjugated, dual MMP2 (matrix metalloproteinase 2) and ADAM8 (a disintegrin and metalloproteinase 8) peptide substrate assay presented herein. The HRP-conjugated substrate is attached to beads through a 6× histidine tag and then incubated with the target enzyme, cleaving the HRP reporter. This product is subsequently removed from the unreacted bound portions of the substrate by magnetic deposition of the beads. The amount of product is then quantified using a standard HRP color development assay employing 3,3′,5,5′-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2). This HRP amplification system represents a new approach to proteinase assays and could be applied to other enzymes, such as lipases, esterases, and kinases, as long as the unreacted substrate can be physically separated from the product and catalysis by the enzyme to be quantified is not impaired dramatically by steric hindrance from the HRP entity. 相似文献
49.
50.
Ulrich Claussen Wanda Zevenboom Uwe Brockmann Dilek Topcu Peter Bot 《Hydrobiologia》2009,629(1):49-58
Eutrophication (nutrient enrichment and subsequent processes) and its adverse ecosystem effects have been discussed as main
issues over the last 20 years in international conferences and conventions for the protection of the marine environment such
as the North Sea Conferences and the 1992 OSPAR Convention (OSPAR; which combined and updated the 1972 Oslo Convention on
dumping waste at the sea and the 1974 Paris Convention on land-based sources of marine pollution). OSPAR committed itself
to reduce phosphorus and nitrogen inputs (in the order of 50% compared with 1985) into the marine areas and ‘to combat eutrophication
to achieve, by the year 2010, a healthy marine environment where eutrophication does not occur’. Within OSPAR, the Comprehensive
Procedure (COMPP) has been developed and used to assess the eutrophication status of the OSPAR maritime area in an harmonised
way. This is based on classification in terms of the following types of areas Non-Problem Areas (no effects), Potential Problem
Areas (not enough data to assess effects) and Problem Areas (effects due to elevated nutrients and/or due to transboundary
transport from adjacent areas). The COMPP consists of a set of harmonised assessment criteria with their area-specific assessment
levels and an integrated area classification approach. The criteria cover all aspects of nutrient enrichment (nutrient inputs,
concentrations and ratios) as well as possible direct effects (e.g. increased levels of nuisance and/or toxic phytoplankton
species, shifts and/or losses of submerged aquatic vegetation) and indirect effects (e.g. oxygen deficiency, changes and/or
death of benthos, death of fish, algal toxins). The COMPP also includes supporting environmental factors. It takes account
of synergies and harmonisation with the EC Water Framework Directive, and has formed a major basis for the EC eutrophication
guidance. Recently, additional components, such as total nitrogen, total phosphorus and transboundary transports have been
included in the assessment of, e.g. the German Bight. The second application of the COMPP resulting in an update of the eutrophication
status of the OSPAR maritime area will be finalised in 2008, and will include the agreed integrated set of Ecological Quality
Objectives (EcoQOs) with respect to eutrophication.
Guest editors: J. H. Andersen & D. J. Conley
Eutrophication in Coastal Ecosystems: Selected papers from the Second International Symposium on Research and Management of
Eutrophication in Coastal Ecosystems, 20–23 June 2006, Nyborg, Denmark 相似文献