全文获取类型
收费全文 | 4354篇 |
免费 | 377篇 |
出版年
2023年 | 15篇 |
2022年 | 13篇 |
2021年 | 75篇 |
2020年 | 31篇 |
2019年 | 64篇 |
2018年 | 69篇 |
2017年 | 53篇 |
2016年 | 129篇 |
2015年 | 205篇 |
2014年 | 252篇 |
2013年 | 292篇 |
2012年 | 406篇 |
2011年 | 342篇 |
2010年 | 240篇 |
2009年 | 186篇 |
2008年 | 254篇 |
2007年 | 250篇 |
2006年 | 238篇 |
2005年 | 209篇 |
2004年 | 193篇 |
2003年 | 153篇 |
2002年 | 163篇 |
2001年 | 81篇 |
2000年 | 57篇 |
1999年 | 64篇 |
1998年 | 37篇 |
1997年 | 33篇 |
1996年 | 28篇 |
1995年 | 42篇 |
1994年 | 31篇 |
1993年 | 21篇 |
1992年 | 51篇 |
1991年 | 45篇 |
1990年 | 34篇 |
1989年 | 30篇 |
1988年 | 23篇 |
1987年 | 19篇 |
1986年 | 26篇 |
1985年 | 27篇 |
1984年 | 26篇 |
1983年 | 16篇 |
1982年 | 13篇 |
1981年 | 17篇 |
1979年 | 21篇 |
1978年 | 15篇 |
1977年 | 14篇 |
1976年 | 17篇 |
1974年 | 18篇 |
1972年 | 11篇 |
1969年 | 10篇 |
排序方式: 共有4731条查询结果,搜索用时 42 毫秒
1.
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
2.
Katrin B?ttger Haralambos Hatzikirou Anja Voss-B?hme Elisabetta Ada Cavalcanti-Adam Miguel A. Herrero Andreas Deutsch 《PLoS computational biology》2015,11(9)
Tumor cells develop different strategies to cope with changing microenvironmental conditions. A prominent example is the adaptive phenotypic switching between cell migration and proliferation. While it has been shown that the migration-proliferation plasticity influences tumor spread, it remains unclear how this particular phenotypic plasticity affects overall tumor growth, in particular initiation and persistence. To address this problem, we formulate and study a mathematical model of spatio-temporal tumor dynamics which incorporates the microenvironmental influence through a local cell density dependence. Our analysis reveals that two dynamic regimes can be distinguished. If cell motility is allowed to increase with local cell density, any tumor cell population will persist in time, irrespective of its initial size. On the contrary, if cell motility is assumed to decrease with respect to local cell density, any tumor population below a certain size threshold will eventually extinguish, a fact usually termed as Allee effect in ecology. These results suggest that strategies aimed at modulating migration are worth to be explored as alternatives to those mainly focused at keeping tumor proliferation under control. 相似文献
3.
4.
Alessandra Apicella Peggy Heunemann Sreenath Bolisetty Matteo Marascio Anja Gemperli Graf Laszlo Garamszegi Raffaele Mezzenga Peter Fischer Christopher J. Plummer Jan-Anders M?nson 《PloS one》2015,10(12)
In a current procedure for periodontal tissue regeneration, enamel matrix derivative (EMD), which is the active component, is mixed with a propylene glycol alginate (PGA) gel carrier and applied directly to the periodontal defect. Exposure of EMD to physiological conditions then causes it to precipitate. However, environmental changes during manufacture and storage may result in modifications to the conformation of the EMD proteins, and eventually premature phase separation of the gel and a loss in therapeutic effectiveness. The present work relates to efforts to improve the stability of EMD-based formulations such as Emdogain™ through the incorporation of arginine, a well-known protein stabilizer, but one that to our knowledge has not so far been considered for this purpose. Representative EMD-buffer solutions with and without arginine were analyzed by 3D-dynamic light scattering, UV-Vis spectroscopy, transmission electron microscopy and Fourier transform infrared spectroscopy at different acidic pH and temperatures, T, in order to simulate the effect of pH variations and thermal stress during manufacture and storage. The results provided evidence that arginine may indeed stabilize EMD against irreversible aggregation with respect to variations in pH and T under these conditions. Moreover, stopped-flow transmittance measurements indicated arginine addition not to suppress precipitation of EMD from either the buffers or the PGA gel carrier when the pH was raised to 7, a fundamental requirement for dental applications. 相似文献
5.
Hairless (H) is the major antagonist within the Notch signalling pathway of Drosophila melanogaster. By binding to Suppressor of Hairless [Su(H)] and two co-repressors, H induces silencing of Notch target genes in the absence of Notch signals. We have applied genomic engineering to create several new H alleles. To this end the endogenous H locus was replaced with an attP site by homologous recombination, serving as a landing platform for subsequent site directed integration of different H constructs. This way we generated a complete H knock out allele H
attP, reintroduced a wild type H genomic and a cDNA-construct (H
gwt, H
cwt) as well as two constructs encoding H proteins defective of Su(H) binding (H
LD, H
iD). Phenotypes regarding viability, bristle and wing development were recorded, and the expression of Notch target genes wingless and cut was analysed in mutant wing discs or in mutant cell clones. Moreover, genetic interactions with Notch (N
5419) and Delta (Dl
B2) mutants were addressed. Overall, phenotypes were largely as expected: both H
LD and H
iD were similar to the H
attP null allele, indicating that most of H activity requires the binding of Su(H). Both rescue constructs H
gwt and H
cwt were homozygous viable without phenotype. Unexpectedly, the hemizygous condition uncovered that they were not identical to the wild type allele: notably H
cwt showed a markedly reduced activity, suggesting the presence of as yet unidentified regulatory or stabilizing elements in untranslated regions of the H gene. Interestingly, H
gwt homozygous cells expressed higher levels of H protein, perhaps unravelling gene-by-environment interactions. 相似文献
6.
Ektoras Hadjipanayi Peer-Hendrik Kuhn Philipp Moog Anna-Theresa Bauer Haydar Kuekrek Lilit Mirzoyan Anja Hummel Katharina Kirchhoff Burak Salgin Sarah Isenburg Ulf Dornseifer Milomir Ninkovic Hans-Günther Machens Arndt F. Schilling 《PloS one》2015,10(8)
Conceptually, premature initiation of post-wound angiogenesis could interfere with hemostasis, as it relies on fibrinolysis. The mechanisms facilitating orchestration of these events remain poorly understood, however, likely due to limitations in discerning the individual contribution of cells and extracellular matrix. Here, we designed an in vitro Hemostatic-Components-Model (HCM) to investigate the role of the fibrin matrix as protein factor-carrier, independent of its cell-scaffold function. After characterizing the proteomic profile of HCM-harvested matrix releasates, we demonstrate that the key pro-/anti-angiogenic factors, VEGF and PF4, are differentially bound by the matrix. Changing matrix fibrin mass consequently alters the balance of releasate factor concentrations, with differential effects on basic endothelial cell (EC) behaviors. While increasing mass, and releasate VEGF levels, promoted EC chemotactic migration, it progressively inhibited tube formation, a response that was dependent on PF4. These results indicate that the clot’s matrix component initially serves as biochemical anti-angiogenic barrier, suggesting that post-hemostatic angiogenesis follows fibrinolysis-mediated angiogenic disinhibition. Beyond their significance towards understanding the spatiotemporal regulation of wound healing, our findings could inform the study of other pathophysiological processes in which coagulation and angiogenesis are prominent features, such as cardiovascular and malignant disease. 相似文献
7.
Olivia Sveidahl Johansen Tao Ma Jakob Bondo Hansen Lasse Kruse Markussen Renate Schreiber Laia Reverte-Salisa Hua Dong Dan Ploug Christensen Wenfei Sun Thorsten Gnad Iuliia Karavaeva Thomas Svava Nielsen Sander Kooijman Cheryl Cero Oksana Dmytriyeva Yachen Shen Maria Razzoli Shannon L. O’Brien Zachary Gerhart-Hines 《Cell》2021,184(13):3502-3518.e33
8.
Hydrobiologia - To observe effects on the phosphorus retention mechanisms of a lake after re-colonisation by macrophytes, Potamogeton crispus L. and Elodea canadensis Michx. were planted in lab... 相似文献
9.
Rebecca C. Schreiber Stacey A. Vaccariello Kristen Boeshore Annette M. Shadiack Richard E. Zigmond 《Developmental neurobiology》2002,53(1):68-79
Transecting the axons of neurons in the adult superior cervical ganglion (SCG; axotomy) results in the survival of most postganglionic neurons, the influx of circulating monocytes, proliferation of satellite cells, and changes in neuronal gene expression. In contrast, transecting the afferent input to the SCG (decentralization) results in nerve terminal degeneration and elicits a different pattern of gene expression. We examined the effects of decentralization on macrophages in the SCG and compared the results to those previously obtained after axotomy. Monoclonal antibodies were used to identify infiltrating (ED1+) and resident (ED2+) macrophages, as well as macrophages expressing MHC class II molecules (OX6+). Normal ganglia contained ED2+ cells and OX6+ cells, but few infiltrating macrophages. After decentralization, the number of infiltrating ED1+ cells increased in the SCG to a density about twofold greater than that previously seen after axotomy. Both the densities of ED2+ and OX6+ cells were essentially unchanged after decentralization, though a large increase in OX6+ cells occurred after axotomy. Proliferation among the ganglion's total non‐neuronal cell population was examined and found to increase about twofold after decentralization and about fourfold after axotomy. Double‐labeling experiments indicated that some of these proliferating cells were macrophages. After both surgical procedures, the percentage of proliferating ED2+ macrophages increased, while neither procedure altered the proliferation of ED1+ macrophages. Axotomy, though not decentralization, increased the proliferation of OX6+ cells. Future studies must address what role(s) infiltrating and/or resident macrophages play in regions of decentralized and axotomized neurons and, if both are involved, whether they play distinct roles. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 68–79, 2002 相似文献
10.