全文获取类型
收费全文 | 7547篇 |
免费 | 702篇 |
国内免费 | 6篇 |
出版年
2023年 | 51篇 |
2022年 | 118篇 |
2021年 | 235篇 |
2020年 | 153篇 |
2019年 | 184篇 |
2018年 | 181篇 |
2017年 | 162篇 |
2016年 | 213篇 |
2015年 | 366篇 |
2014年 | 395篇 |
2013年 | 478篇 |
2012年 | 564篇 |
2011年 | 551篇 |
2010年 | 328篇 |
2009年 | 301篇 |
2008年 | 390篇 |
2007年 | 400篇 |
2006年 | 340篇 |
2005年 | 344篇 |
2004年 | 320篇 |
2003年 | 284篇 |
2002年 | 274篇 |
2001年 | 77篇 |
2000年 | 52篇 |
1999年 | 68篇 |
1998年 | 94篇 |
1997年 | 41篇 |
1996年 | 35篇 |
1995年 | 39篇 |
1994年 | 32篇 |
1993年 | 43篇 |
1992年 | 44篇 |
1991年 | 30篇 |
1990年 | 31篇 |
1989年 | 41篇 |
1988年 | 30篇 |
1987年 | 39篇 |
1986年 | 33篇 |
1985年 | 28篇 |
1984年 | 38篇 |
1982年 | 44篇 |
1981年 | 45篇 |
1980年 | 42篇 |
1979年 | 24篇 |
1978年 | 39篇 |
1977年 | 29篇 |
1976年 | 24篇 |
1975年 | 33篇 |
1974年 | 30篇 |
1973年 | 29篇 |
排序方式: 共有8255条查询结果,搜索用时 15 毫秒
1.
Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ann M. Toth Patricia Devaux Roberto Cattaneo Charles E. Samuel 《Journal of virology》2009,83(2):961-968
The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKRkd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (Cko) virus but had no effect on the growth of either wild-type (WT) or V knockout (Vko) virus. Increased growth of the Cko virus in PKRkd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, Vko, or especially Cko virus caused significantly less apoptosis in PKRkd cells than in PKR-sufficient cells. Although apoptosis induced by Cko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of Cko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR. 相似文献
2.
3.
4.
5.
Laura W. Pomeroy Jacob M. Aaronson Samuel Handelman Jori Hardman Kevin Kawalec Thomas Bitterman Ward C. Wheeler 《Cladistics : the international journal of the Willi Hennig Society》2012,28(5):483-488
We have reported previously on use of a web‐based application, Supramap ( http://supramap.org ) for the study of biogeographic, genotypic, and phenotypic evolution. Using Supramap we have developed maps of the spread of drug‐resistant influenza and host shifts in H1N1 and H5N1 influenza and coronaviruses such as SARS. Here we report on another zoonotic pathogen, H7 influenza, and provide an update on the implementation of Supramap as a web service. We find that the emergence of pathogenic strains of H7 is labile with many transitions from high to low pathogenicity, and from low to high pathogenicity. We use Supramap to put these events in a temporal and geospatial context. We identify several lineages of H7 influenza with biomarkers of high pathogenicity in regions that have not been reported in the scientific literature. The original implementation of Supramap was built with tightly coupled client and server software. Now we have decoupled the components to provide a modular web service for POY ( http://poyws.org ) that can be consumed by a data provider to create a novel application. To demonstrate the web service, we have produced an application, Geogenes ( http://geogenes.org ). Unlike in Supramap, in which the user is required to create and upload data files, in Geogenes the user works from a graphical interface to query an underlying dataset. Geogenes demonstrates how the web service can provide underlying processing for any sequence and metadata database. © The Willi Hennig Society 2012. 相似文献
6.
Anthony J. Hesketh Caroline Maloney Christopher A. Behr Morris C. Edelman Richard D. Glick Yousef Al-Abed Marc Symons Samuel Z. Soffer Bettie M. Steinberg 《PloS one》2015,10(12)
Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma. 相似文献
7.
Christelle Hély Kelly K. Caylor Peter Dowty Samuel Alleaume Robert J. Swap Hank H. Shugart Christopher O. Justice 《Ecosystems》2007,10(7):1116-1132
Abstract
We present a regional fuel load model (1 km2 spatial resolution) applied in the southern African savanna region. The model is based on a patch-scale production efficiency
model (PEM) scaled up to the regional level using empirical relationships between patch-scale behavior and multi-source remote
sensing data (spatio-temporal variability of vegetation and climatic variables). The model requires the spatial distribution
of woody vegetation cover, which is used to determine separate respiration rates for tree and grass. Net primary production,
grass and tree leaf death, and herbivory are also taken into account in this mechanistic modeling approach. The fuel load
model has been calibrated and validated from independent measurements taken from savanna vegetation in Africa southward from
the equator. A sensitivity analysis on the effect of climate variables (incoming radiation, air temperature, and precipitation)
has been conducted to demonstrate the strong role that water availability has in determining productivity and subsequent fuel
load over the southern African region. The model performance has been tested in four different areas representative of a regional
increasing rainfall gradient—Etosha National Park, Namibia, Mongu and Kasama, Zambia, as well as in Kruger National Park,
South Africa. Within each area, we analyze model output from three different magnitudes of canopy coverage (<5, 30, and 50%).
We find that fuel load ranges predicted by the model are globally in agreement with field measurements for the same year.
High rainfall sustains green herbaceous production late in the dry season and delays tree leaf litter production. Effect of
water on production varies across the rainfall gradient with delayed start of green material production in more arid regions. 相似文献
8.
James J. Krupa Kevin R. Hopper Samuel B. Gruber Jason M. Schmidt James D. Harwood 《Ecology and evolution》2020,10(11):4762-4772
- Plant–animal interactions are diverse and widespread shaping ecology, evolution, and biodiversity of most ecological communities. Carnivorous plants are unusual in that they can be simultaneously engaged with animals in multiple mutualistic and antagonistic interactions including reversed plant–animal interactions where they are the predator. Competition with animals is a potential antagonistic plant–animal interaction unique to carnivorous plants when they and animal predators consume the same prey.
- The goal of this field study was to test the hypothesis that under natural conditions, sundews and spiders are predators consuming the same prey thus creating an environment where interkingdom competition can occur.
- Over 12 months, we collected data on 15 dates in the only protected Highland Rim Wet Meadow Ecosystem in Kentucky where sundews, sheet‐web spiders, and ground‐running spiders co‐exist. One each sampling day, we attempted to locate fifteen sites with: (a) both sheet‐web spiders and sundews; (b) sundews only; and (c) where neither occurred. Sticky traps were set at each of these sites to determine prey (springtails) activity–density. Ground‐running spiders were collected on sampling days. DNA extraction was performed on all spiders to determine which individuals had eaten springtails and comparing this to the density of sundews where the spiders were captured.
- Sundews and spiders consumed springtails. Springtail activity–densities were lower, the higher the density of sundews. Both sheet‐web and ground‐running spiders were found less often where sundew densities were high. Sheet‐web size was smaller where sundew densities were high.
- The results of this study suggest that asymmetrical exploitative competition occurs between sundews and spiders. Sundews appear to have a greater negative impact on spiders, where spiders probably have little impact on sundews. In this example of interkingdom competition where the asymmetry should be most extreme, amensalism where one competitor experiences no cost of interaction may be occurring.
9.
E. Schuettpelz S. B. Hoot R. Samuel F. Ehrendorfer 《Plant Systematics and Evolution》2002,231(1-4):143-151
Using two molecular data sets, the plastid atpB-rbcL intergenic spacer region and the nuclear ribosomal internal transcribed spacer regions (ITS), the taxonomic affinities of
two newly available Anemone species from the Southern Hemisphere were tested. From previous work based on morphology and geographic distribution, it
was assumed that A. tenuicaulis from New Zealand was most closely related to the Tasmanian A. crassifolia, whereas the affinity of A. antucensis from Chile and Argentina was regarded as uncertain. Analyses of molecular sequence data from these and 18 other species of
Anemone s.lat. (with Clematis as outgroup) result in trees largely congruent with past analyses based on morphology and plastid restriction site data.
They strongly support A. richardsonii and A. canadensis (with boreal distributions in the Northern Hemisphere) as paraphyletic to a well supported Southern Hemisphere clade consisting
of A. antucensis and A. tenuicaulis. This group of four species is part of an otherwise predominantly Northern Hemisphere assemblage (subgenus Anemonidium s.lat., chromosome base number x=7), including A. narcissiflora, A. obtusiloba, A. keiskeana and A. (=Hepatica) americana. All other austral species included in the present sampling, A. crassifolia (Tasmania), A. knowltonia (=Knowltonia capensis), and A. caffra (both South African), form a separate clade, sister to A. (=Pulsatilla) occidentalis and other Northern Hemisphere anemones (subgenus Anemone s.lat., x=8). Possible phytogeographical links of the Southern Hemisphere species are discussed.
Received April 23, 2001 Accepted October 4, 2001 相似文献
10.
Planar cell polarity (PCP) controls the orientation of cells within tissues and the polarized outgrowth of cellular appendages. So far, six PCP core proteins including the transmembrane proteins Frizzled (Fz), Strabismus (Stbm) and Flamingo (Fmi) have been identified. These proteins form asymmetric PCP domains at apical junctions of epithelial cells. Here, we demonstrate that VhaPRR, an accessory subunit of the proton pump V‐ATPase, directly interacts with the protocadherin Fmi through its extracellular domain. It also shows a striking co‐localization with PCP proteins during all pupal wing stages in Drosophila. This localization depends on intact PCP domains. Reversely, VhaPRR is required for stable PCP domains, identifying it as a novel PCP core protein. VhaPRR performs an additional role in vesicular acidification as well as endolysosomal sorting and degradation. Membrane proteins, such as E‐Cadherin and the Notch receptor, accumulate at the surface and in intracellular vesicles of cells mutant for VhaPRR. This trafficking defect is shared by other V‐ATPase subunits. By contrast, the V‐ATPase does not seem to have a direct role in PCP regulation. Together, our results suggest two roles for VhaPRR, one for PCP and another in endosomal trafficking. This dual function establishes VhaPRR as a key factor in epithelial morphogenesis. 相似文献