全文获取类型
收费全文 | 11326篇 |
免费 | 837篇 |
国内免费 | 3篇 |
出版年
2023年 | 70篇 |
2022年 | 138篇 |
2021年 | 277篇 |
2020年 | 173篇 |
2019年 | 196篇 |
2018年 | 350篇 |
2017年 | 286篇 |
2016年 | 413篇 |
2015年 | 599篇 |
2014年 | 666篇 |
2013年 | 838篇 |
2012年 | 948篇 |
2011年 | 945篇 |
2010年 | 587篇 |
2009年 | 497篇 |
2008年 | 679篇 |
2007年 | 599篇 |
2006年 | 607篇 |
2005年 | 544篇 |
2004年 | 452篇 |
2003年 | 440篇 |
2002年 | 448篇 |
2001年 | 137篇 |
2000年 | 125篇 |
1999年 | 122篇 |
1998年 | 134篇 |
1997年 | 101篇 |
1996年 | 73篇 |
1995年 | 62篇 |
1994年 | 54篇 |
1993年 | 45篇 |
1992年 | 69篇 |
1991年 | 50篇 |
1990年 | 54篇 |
1989年 | 54篇 |
1988年 | 51篇 |
1987年 | 27篇 |
1986年 | 31篇 |
1985年 | 26篇 |
1984年 | 24篇 |
1983年 | 23篇 |
1982年 | 24篇 |
1981年 | 28篇 |
1980年 | 15篇 |
1979年 | 16篇 |
1978年 | 8篇 |
1977年 | 8篇 |
1974年 | 7篇 |
1973年 | 8篇 |
1971年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 22 毫秒
1.
2.
Laura Cernat Cristina Blaj Rene Jackstadt Lydia Brandl Jutta Engel Heiko Hermeking Andreas Jung Thomas Kirchner David Horst 《PloS one》2014,9(8)
Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes. 相似文献
3.
The role of arctic zooplankton in biogeochemical cycles: respiration and excretion of ammonia and phosphate during summer 总被引:1,自引:0,他引:1
M. Alcaraz R. Almeda A. Calbet E. Saiz C. M. Duarte S. Lasternas S. Agustí R. Santiago J. Movilla A. Alonso 《Polar Biology》2010,33(12):1719-1731
The study of the structural and functional properties of key components of polar marine ecosystems has received increased
attention in order to better understand the ecological consequences of future sea temperature rise and seasonal ice retraction.
Owing to this purpose, during the ATOS-Arctic cruise, held in July 2007 in the framework of the 2007–2008 International Polar
Year, we studied the respiratory carbon demand of mesozooplankton as well as their contribution to the regeneration of inorganic
nitrogen and phosphorus (NH4-N and PO4-P) via excretion. The studied area comprised several stations along a latitudinal gradient in the East Greenland current, plus a
network of stations NW of the Svalbard islands. The specific respiratory carbon losses and phosphorus (PO4-P) excretion rates were similar or slightly higher than some reports for Arctic mesozooplankton, but the nitrogen (NH4-N) excretion rates were higher by a factor of 3 when compared with previous data sets. The mesozooplankton respiratory losses
were equivalent to 23% of primary production, and at turn zooplankton contributed by excretion to more than 50% of the N and
P required by phytoplankton. Although C:N, C:P and N:P metabolic atomic quotients almost coincided with the average Redfield’s
stoichiometric ratios, the low C:N values when compared to previous reports suggested a predominance of protein-related metabolic
substrates. The potential consequences of changes observed in the C:N, N:P and C:P metabolic ratios of mesozooplankton for
Arctic marine ecosystems are discussed. 相似文献
4.
Francisco Gutirrez‐Corchero M. Victoria Arruga Lourdes Sanz Cristina García M. Angeles Hernndez Francisco Campos 《Molecular ecology resources》2002,2(1):75-77
FTA® cards were used for long‐term storage of avian blood samples. Blood DNA was extracted by a simple method and used in PCR for sex identification of adult and nestling Great Grey Shrikes Lanius excubitor. 相似文献
5.
Ho WW Fernandes CC Alves-Gomes JA Smith GT 《Ethology : formerly Zeitschrift fur Tierpsychologie》2010,116(11):1050-1064
The South American weakly-electric knifefish (Apteronotidae) produce highly diverse and readily quantifiable electrocommunication signals. The electric organ discharge frequency (EODf), and EOD modulations (chirps and gradual frequency rises (GFRs)), vary dramatically across sexes and species, presenting an ideal opportunity to examine the proximate and ultimate bases of sexually dimorphic behavior. We complemented previous studies on the sexual dimorphism of apteronotid communication signals by investigating electric signal features and their hormonal correlates in Apteronotus bonapartii, a species which exhibits strong sexual dimorphism in snout morphology. Electrocommunication signals were evoked and recorded using a playback paradigm, and were analyzed for signal features including EOD frequency and the structure of EOD modulations. To investigate the androgenic correlates of sexually dimorphic EOD signals, we measured plasma concentrations of testosterone and 11-ketotestosterone. A. bonapartii responded robustly to stimulus playbacks. EODf was sexually monomorphic, and males and females produced chirps with similar durations and amounts of frequency modulation. However, males were more likely than females to produce chirps with multiple frequency peaks. Sexual dimorphism in apteronotid electrocommunication signals appears to be highly evolutionarily labile. Extensive interspecific variation in the magnitude and direction of sex differences in EODf and in different aspects of chirp structure suggest that chirp signals may be an important locus of evolutionary change within the clade. The weakly-electric fish represent a rich source of data for understanding the selective pressures that shape, and the neuroendocrine mechanisms that underlie, diversity in the sexual dimorphism of behavior. 相似文献
6.
Rafael Ricci-Azevedo Aline Ferreira Oliveira Marina C. A. V. Conrado Fernanda Caroline Carvalho Maria Cristina Roque-Barreira 《PLoS neglected tropical diseases》2016,10(4)
ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) release; otherwise, transforming growth factor-beta (TGF-β) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an appropriate molecular template for the construction of an efficient anti-infective agent. 相似文献
7.
Marta Tejera-Alhambra Armanda Casrouge Clara de Andrés Ansgar Seyfferth Rocío Ramos-Medina Bárbara Alonso Janet Vega Lidia Fernández-Paredes Matthew L. Albert Silvia Sánchez-Ramón 《PloS one》2015,10(6)
Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients. 相似文献
8.
We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote “healthy” chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects. 相似文献
9.
10.
Adriana Calderaro Giovanna Piccolo Chiara Gorrini Sara Montecchini Sabina Rossi Maria Cristina Medici Carlo Chezzi Georges Snounou 《PloS one》2012,7(10)
It has been proposed that ovale malaria in humans is caused by two closely related but distinct species of malaria parasites: P. ovale curtisi and P. ovale wallikeri. We have extended and optimized a Real-time PCR assay targeting the parasite’s small subunit ribosomal RNA (ssrRNA) gene to detect both these species. When the assay was applied to 31 archival blood samples from patients diagnosed with P. ovale, it was found that the infection in 20 was due to P. ovale curtisi and in the remaining 11 to P. ovale wallikeri. Thus, this assay provides a useful tool that can be applied to epidemiological investigations of the two newly recognized distinct P. ovale species, that might reveal if these species also differ in their clinical manifestation, drugs susceptibility and relapse periodicity. The results presented confirm that P. ovale wallikeri is not confined to Southeast Asia, since the majority of the patients analyzed in this study had acquired their P. ovale infection in African countries, mostly situated in West Africa. 相似文献