全文获取类型
收费全文 | 534篇 |
免费 | 17篇 |
出版年
2022年 | 2篇 |
2021年 | 11篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 13篇 |
2015年 | 17篇 |
2014年 | 17篇 |
2013年 | 24篇 |
2012年 | 45篇 |
2011年 | 33篇 |
2010年 | 20篇 |
2009年 | 33篇 |
2008年 | 30篇 |
2007年 | 33篇 |
2006年 | 32篇 |
2005年 | 25篇 |
2004年 | 29篇 |
2003年 | 17篇 |
2002年 | 17篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 9篇 |
1998年 | 12篇 |
1997年 | 8篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 8篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 6篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 2篇 |
1984年 | 9篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1970年 | 4篇 |
1969年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有551条查询结果,搜索用时 140 毫秒
91.
Abigael Eva Chaouat Hagit Achdout Inbal Kol Orit Berhani Gil Roi Einat B. Vitner Sharon Melamed Boaz Politi Eran Zahavy Ilija Brizic Tihana Lenac Rovis Or Alfi Dana Wolf Stipan Jonjic Tomer Israely Ofer Mandelboim 《PLoS pathogens》2021,17(12)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Currently, as dangerous mutations emerge, there is an increased demand for specific treatments for SARS-CoV-2 infected patients. The spike glycoprotein on the virus envelope binds to the angiotensin converting enzyme 2 (ACE2) on host cells through its receptor binding domain (RBD) to mediate virus entry. Thus, blocking this interaction may inhibit viral entry and consequently stop infection. Here, we generated fusion proteins composed of the extracellular portions of ACE2 and RBD fused to the Fc portion of human IgG1 (ACE2-Ig and RBD-Ig, respectively). We demonstrate that ACE2-Ig is enzymatically active and that it can be recognized by the SARS-CoV-2 RBD, independently of its enzymatic activity. We further show that RBD-Ig efficiently inhibits in-vivo SARS-CoV-2 infection better than ACE2-Ig. Mechanistically, we show that anti-spike antibody generation, ACE2 enzymatic activity, and ACE2 surface expression were not affected by RBD-Ig. Finally, we show that RBD-Ig is more efficient than ACE2-Ig at neutralizing high virus titers. We thus propose that RBD-Ig physically blocks virus infection by binding to ACE2 and that RBD-Ig should be used for the treatment of SARS-CoV-2-infected patients. 相似文献
92.
Aims Resource allocation in plants can be strongly affected by competition. Besides plant–plant interactions, terrestrial plants compete with the soil bacterial community over nutrients. Since the bacterial communities cannot synthesize their own energy sources, they are dependent on external carbon sources. Unlike the effect of overall amounts of carbon (added to the soil) on plant performance, the effect of fine scale temporal variation in soil carbon inputs on the bacterial biomass and its cascading effects on plant growth are largely unknown. We hypothesize that continuous carbon supply (small temporal variance) will result in a relatively constant bacterial biomass that will effectively compete with plants for nutrients. On the other hand, carbon pulses (large temporal variance) are expected to cause oscillations in bacterial biomass, enabling plants temporal escape from competition and possibly enabling increased growth. We thus predicted that continuous carbon supply would increase root allocation at the expense of decreased reproductive output. We also expected this effect to be noticeable only when sufficient nutrients were present in the soil.Methods Wheat plants were grown for 64 days in pots containing either sterilized or inoculated soils, with or without slow-release fertilizer, subjected to one of the following six carbon treatments: daily (1.5mg glucose), every other day (3mg glucose), 4 days (6mg glucose), 8 days (12mg glucose), 16 days (24mg glucose) and no carbon control.Important findings Remarkably, carbon pulses (every 2–16 days) led to increased reproductive allocation at the expense of decreased root allocation in plants growing in inoculated soils. Consistent with our prediction, these effects were noticeable only when sufficient nutrients were present in the soil. Furthermore, soil inoculation in plants subjected to low nutrient availability resulted in decreased total plant biomass. We interpret this to mean that when the amount of available nutrients is low, these nutrients are mainly used by the bacterial community. Our results show that temporal variation in soil carbon inputs may play an important role in aboveground–belowground interactions, affecting plant resource allocation. 相似文献
93.
The present study compares gonad structure and oogenesis in 30 species of cardinal fish (Apogonidae) from the Indo-Pacific
region. In all of the species studied the ovaries are bilobed, with each lobe possessing ovigerous lamellae whose numbers
and dimensions increase concomitantly with growth of the fish and reproductive stage, and correlate with the total dimensions
of the particular species. In species of the genus Siphamia, the ovarian lobes are associated with a fat body that is not found in species of the other genera studied. Some of the species
studied (Siphamia spp.; Archamia spp.) demonstrate group-synchronized maturation of eggs, possibly with only one spawn per reproduction season. However, most
of the Apogon spp., and other genera, have unsynchronized cycles, a characteristic of multiple spawners. The various stages of previtellogenic
and vitellogenic development are similar in the different species, but differ in timing and dimensions of the oocytes around
which the morphogenesis of the egg envelope (chorion) and follicle begins. Differentiation of the egg envelope and follicle
cells parallels the vitellogenic stages of egg development. The number of eggs was found to correlate positively with the
length of the body and ovary of the fish, whereas egg diameter was found to correlate negatively with body length. The surface
of the egg envelope bears ridges that form patterns of various types, whose structures and dimensions seem to be species-specific,
and which in most species converge upon the single micropyle on the animal pole. The exposed ridge mazes include a special
fibrous web that anchors in the micropyle. The production and importance of these ridges, as well as the correlations between
egg numbers per spawn, egg dimensions, and the oral dimensions of the paternal male, are discussed. 相似文献
94.
We observed patch-use behavior by two gerbil species in a fieldsetting and investigated how aggression and intrinsic decision-makinginteract to influence patch residence times. Results were interpretedby using a competing risk analysis model, which uniquely enabledus to estimate the intrinsic patch-leaving decisions independentlyof external interruptions of foraging bouts by aggression. Theexperiment was conducted in two 1-ha field enclosures completelysurrounded by rodent-proof fences and included allopatric (onlyGerbillus andersoni allenbyi) and sympatric (G. a. allenbyiand G. pyramidum) treatments. We predicted that increased foodpatch quality (i.e., habitat quality) should decrease intrinsicpatch-leaving rates and increase rates of aggressive interactionsinvolving the forager feeding in the patch (i.e., the occupantindividual). We also anticipated that increasing populationdensity should result in an increase in the rate of aggressiveinteractions involving the occupant individual. Our resultssupported the first two predictions, indicating a trade-offbetween foraging and aggression. However, the third predictionwas realized only for G. a. allenbyi in allopatry. Furthermore,in allopatry, occupant G. a. allenbyi individuals with highcompetitive ranks were involved in aggressive interactions atlower rates than those with low competitive ranks. However,in sympatry, patch-use behavior of occupant G. a. allenbyi individualswas mainly influenced by aggressive behavior of G. pyramidum,which did not respond to their competitive rank. Thus, it shouldpay less for G. a. allenbyi to be aggressive in sympatric populations.The observed reduction in intraspecific aggression among individualG. a. allenbyi in the presence of G. pyramidum supports thisassertion. We suggest that this reduction likely weakens thenegative effect of intra- and interspecific density on the percapita growth rate of G. a. allenbyi. Because this would changethe slope of the isocline of G. a. allenbyi, it could be animportant mechanism promoting coexistence when habitat selectionis constrained. 相似文献
95.
This study examined p27 expression in a cohort of salivary malignancies (n = 74) for a prolonged period (20 years). Reduction of p27 expression was found to be a most powerful predictor for poor survival
and more so when the tumor concurrently expressed high levels of p53, TUNEL and heparanase markers, dramatically dropping
the patient survival probability to 0! While no patient whose tumor-staining profile included: p27 > 50%, p53 = 0, TUNEL = 0
and heparanase = 0, died of the disease during the 20-year follow up, the median of survival of the group with p27 ≤ 50%,
p53 > 0, TUNEL > 0 and heparanase > 0 was only 39 months. The survival probabilities of these two groups at 5 years were 100
and 50%, respectively, and at 20 years they were 100 and 0%, respectively (P = 0.05). Significant p27 reduction also resulted in significantly larger tumor size (T value), higher spread of neck metastasis and extra capsular spread and in more advanced disease (higher stage). Significant
correlation rates were found between age and poor survival, age and reduced p27 expression, and reduced p27 expression and
other general co-existing malignancies, indicating p27 reduction as part of a general phenomenon—age related mutagenesis.
Significantly more extensive therapy applied to patients with salivary reduced-p27 tumors could not prevent the rise in mortality
rate, questioning the justification for extensive therapy which is naturally accompanied by higher morbidity. Additional therapeutic
tools for fighting salivary cancer, possibly based on the new understanding of the p27, p53, TUNEL and heparanase carcinogenic
network, are necessary. 相似文献
96.
97.
Hua Su Melissa de Vries Stephen Wanyonyi David Segal Ofer Reizes Louise J. Hutley Jonathan P. Whitehead 《Biochemical and biophysical research communications》2009,386(2):351-171
We previously described a putative role for inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme in de novo guanine nucleotide biosynthesis, in lipid accumulation. Here we present data which demonstrate that IMPDH activity is required for differentiation of preadipocytes into mature, lipid-laden adipocytes and maintenance of adipose tissue mass. In 3T3-L1 preadipocytes inhibition of IMPDH with mycophenolic acid (MPA) reduced intracellular GTP levels by 60% (p < 0.05) and blocked adipogenesis (p < 0.05). Co-treatment with guanosine, a substrate in the salvage pathway of nucleotide biosynthesis, restored GTP levels and adipogenesis demonstrating the specificity of these effects. Treatment of diet-induced obese mice with mycophenolate mofetil (MMF), the prodrug of MPA, for 28 days did not affect food intake or lean body mass but reduced body fat content (by 36%, p = 0.002) and adipocyte size (p = 0.03) and number. These data suggest that inhibition of IMPDH may represent a novel strategy to reduce adipose tissue mass. 相似文献
98.
Warshakoon NC Sheville J Bhatt RT Ji W Mendez-Andino JL Meyers KM Kim N Wos JA Mitchell C Paris JL Pinney BB Reizes O Hu XE 《Bioorganic & medicinal chemistry letters》2006,16(19):5207-5211
A novel series of substituted quinoline analogs were designed and synthesized as potent and selective melanin concentrating hormone (MCH) antagonists. These analogs show potent (nM) activity (12a-k) with a moderate selectivity. Conversely, the conformationally constrained thienopyrimidinone analogs (18a-g) showed improved activity in MCH-1R and selectivity over 5HT2C. 相似文献
99.
Tobias Strunk Melanie R. Power Coombs Andrew J. Currie Peter Richmond Douglas T. Golenbock Liat Stoler-Barak Leighanne C. Gallington Michael Otto David Burgner Ofer Levy 《PloS one》2010,5(4)
Background
Staphylococcus epidermidis (SE) is a nosocomial pathogen that causes catheter-associated bacteremia in the immunocompromised, including those at the extremes of age, motivating study of host clearance mechanisms. SE-derived soluble components engage TLR2; but additional signaling pathways have also been implicated, and TLR2 can play complex, at times detrimental, roles in host defense against other Staphylococcal spp. The role of TLR2 in responses of primary blood leukocytes to live SE and in clearance of SE bacteremia, the most common clinical manifestation of SE infection, is unknown.Methodology/Principal Findings
We studied TLR2-mediated recognition of live clinical SE strain 1457 employing TLR2-transfected cells, neutralizing anti-TLR antibodies and TLR2-deficient mice. TLR2 mediated SE-induced cytokine production in human embryonic kidney cells, human whole blood and murine primary macrophages, in part via recognition of a soluble TLR2 agonist. After i.v. challenge with SE, early (1 h) cytokine/chemokine production and subsequent clearance of bacteremia (24–48 h) were markedly impaired in TLR2-deficient mice.Conclusions/Significance
TLR2 mediates recognition of live SE and clearance of SE bacteremia in vivo. 相似文献100.
Small‐scale spatial variability in the distribution of ectomycorrhizal fungi affects plant performance and fungal diversity 下载免费PDF全文
Stav Livne‐Luzon Ofer Ovadia Gil Weber Yael Avidan Hen Migael Sydney I. Glassman Thomas D. Bruns Hagai Shemesh 《Ecology letters》2017,20(9):1192-1202
The effects of spatial heterogeneity in negative biological interactions on individual performance and species diversity have been studied extensively. However, little is known about the respective effects involving positive biological interactions, including the symbiosis between plants and ectomycorrhizal (EM) fungi. Using a greenhouse bioassay, we explored how spatial heterogeneity of natural soil inoculum influences the performance of pine seedlings and composition of their root‐associated EM fungi. When the inoculum was homogenously distributed, a single EM fungal taxon dominated the roots of most pine seedlings, reducing the diversity of EM fungi at the treatment level, while substantially improving pine seedling performance. In contrast, clumped inoculum allowed the proliferation of several different EM fungi, increasing the overall EM fungal diversity. The most dominant EM fungal taxon detected in the homogeneous treatment was also a highly beneficial mutualist, implying that the trade‐off between competitive ability and mutualistic capacity does not always exist. 相似文献