全文获取类型
收费全文 | 9563篇 |
免费 | 865篇 |
国内免费 | 14篇 |
出版年
2023年 | 40篇 |
2022年 | 105篇 |
2021年 | 225篇 |
2020年 | 118篇 |
2019年 | 146篇 |
2018年 | 172篇 |
2017年 | 151篇 |
2016年 | 264篇 |
2015年 | 439篇 |
2014年 | 453篇 |
2013年 | 588篇 |
2012年 | 765篇 |
2011年 | 682篇 |
2010年 | 440篇 |
2009年 | 462篇 |
2008年 | 597篇 |
2007年 | 544篇 |
2006年 | 544篇 |
2005年 | 477篇 |
2004年 | 477篇 |
2003年 | 458篇 |
2002年 | 407篇 |
2001年 | 131篇 |
2000年 | 110篇 |
1999年 | 109篇 |
1998年 | 98篇 |
1997年 | 62篇 |
1996年 | 62篇 |
1995年 | 56篇 |
1994年 | 65篇 |
1993年 | 58篇 |
1992年 | 79篇 |
1991年 | 61篇 |
1990年 | 61篇 |
1989年 | 66篇 |
1988年 | 57篇 |
1987年 | 46篇 |
1986年 | 47篇 |
1985年 | 37篇 |
1984年 | 48篇 |
1983年 | 54篇 |
1982年 | 34篇 |
1981年 | 43篇 |
1980年 | 40篇 |
1979年 | 55篇 |
1977年 | 32篇 |
1976年 | 36篇 |
1975年 | 32篇 |
1974年 | 37篇 |
1973年 | 30篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Characterization of human immunodeficiency virus type 1 integrase expressed in Escherichia coli and analysis of variants with amino-terminal mutations. 总被引:43,自引:30,他引:13
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)
Replication of a retroviral genome depends upon integration of the viral DNA into a chromosome of the host cell. The integration reaction is mediated by integrase, a viral enzyme. Human immunodeficiency virus type 1 integrase was expressed in Escherichia coli and purified to near homogeneity. Optimum conditions for the integration and 3'-end-processing activities of integrase were characterized by using an in vitro assay with short, double-stranded oligonucleotide substrates. Mutants containing amino acid substitutions within the HHCC region, defined by phylogenetically conserved pairs of histidine and cysteine residues near the N terminus, were constructed and characterized by using three assays: 3'-end processing, integration, and the reverse of the integration reaction (or disintegration). Mutations in the conserved histidine and cysteine residues abolished both integration and processing activities. Weak activity in both assays was retained by two other mutants containing substitutions for less highly conserved amino acids in this region. All mutants retained activity in the disintegration assay, implying that the active site for DNA cleavage-ligation is not located in this domain and that the HHCC region is not the sole DNA-binding domain in the protein. However, the preferential impairment of processing and integration rather than disintegration by mutations in the HHCC region is consistent with a role for this domain in recognizing features of the viral DNA. This hypothesis is supported by the results of disintegration assays performed with altered substrates. The results support a model involving separate viral and target DNA-binding sites on integrase. 相似文献
102.
Louis-Marie Vincent 《Acta biotheoretica》1993,41(1-2):139-145
A new approach to information is proposed with the intention of providing a conceptual tool adapted to biology, including a semantic value.Information involves a material support as well as a significance, adapted to the cognitive domain of the receiver and/or the transmitter. A message does not carry any information, only data. The receiver makes an identification by a procedure of recognition of the forms, which activate previously learned significance. This treatment leads to a new significance (or new knowledge).The notion of a probabilistic event is abandoned. The quantity of information is the product of the quantity of data (probability of recognition of the message) times the value of the significance, determined by its semantic level. 相似文献
103.
The effects of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on the proliferation, protein kinase C activity (PKC), and c-fos gene expression were examined in cultures of young and senescent (90-95% lifespan completed) WI-38 human diploid fibroblasts. We observed that, following stimulation with medium containing 10% fetal bovine serum (FBS), the translocation of PKC from the cytosol to the particulate compartment was less efficient in senescent WI-38 cells than in young cells. However, when PMA was added to the medium, the intracellular distribution of PKC activity in old cells became nearly identical to that observed in young cells. The inducibility of c-fos mRNA by serum addition, which is a protein kinase C-dependent event [64], was significantly amplified in the presence of PMA. Moreover, the duration of peak c-fos expression, after stimulation by FBS and PMA, increased in senescent cells as compared to young cells. Our results reveal that the normal signal transduction pathway is altered in senescent, slowly proliferating human fibroblasts and that it can be partially restored in the presence of the tumor promoter PMA. 相似文献
104.
Marie Arnaud Stefan Krause Richard J. Norby Thuong Huyen Dang Nezha Acil Nicholas Kettridge Vincent Gauci Sami Ullah 《Global Change Biology》2023,29(12):3256-3270
Mangroves are among the most carbon-dense ecosystems worldwide. Most of the carbon in mangroves is found belowground, and root production might be an important control of carbon accumulation, but has been rarely quantified and understood at the global scale. Here, we determined the global mangrove root production rate and its controls using a systematic review and a recently formalised, spatially explicit mangrove typology framework based on geomorphological settings. We found that global mangrove root production averaged ~770 ± 202 g of dry biomass m−2 year−1 globally, which is much higher than previously reported and close to the root production of the most productive tropical forests. Geomorphological settings exerted marked control over root production together with air temperature and precipitation (r2 ≈ 30%, p < .001). Our review shows that individual global changes (e.g. warming, eutrophication, drought) have antagonist effects on root production, but they have rarely been studied in combination. Based on this newly established root production rate, root-derived carbon might account for most of the total carbon buried in mangroves, and 19 Tg C lost in mangroves each year (e.g. as CO2). Inclusion of root production measurements in understudied geomorphological settings (i.e. deltas), regions (Indonesia, South America and Africa) and soil depth (>40 cm), as well as the creation of a mangrove root trait database will push forward our understanding of the global mangrove carbon cycle for now and the future. Overall, this review presents a comprehensive analysis of root production in mangroves, and highlights the central role of root production in the global mangrove carbon budget. 相似文献
105.
When compared to virgin land (forest and grassland), croplands store significantly lower amounts of organic carbon (OC), mainly as a result of soil tillage, and decreased plant inputs to the soil over the whole year. Doubts have been expressed over how much reduced and zero tillage agriculture can increase OC in soils when the whole soil profile is considered. Consequently, cover-crops that are grown in-between crops instead of leaving soils bare appear as the “last man standing” in our quest to enhance cropland OC stocks. Despite the claim by numerous meta-analyses of a mean carbon sequestration rate by cover crops to be as high as 0.32 ± 0.08 ton C ha−1 year−1, the present analysis showed that all of the 37 existing field studies worldwide only sampled to a depth of 30 cm or less and did not compare treatments on the basis of equivalent soil mass. Thirteen studies presented information on OC content only and not on OC stocks, had inappropriate controls (n = 14), had durations of 3 years or lower (n = 5), considered only one to two data points per treatment (n = 4), or used cover crops as cash crops (i.e., grown longer that in-between two crops) instead of catch crops (n = 2), which in all cases constitutes shortcomings. Of the remaining six trials, four showed non-significant trends, one study displayed a negative impact of cover crops, and one study displayed a positive impact, resulting in a mean OC storage of 0.03 ton ha−1 year−1. Models and policies should urgently adapt to such new figure. Finally, more is to be done not only to improve the design of cover-crop studies for reaching sound conclusions but also to understand the underlying reasons of the low efficiency of cover crops for improved carbon sequestration into soils, with possible strategies being suggested. 相似文献
106.
Erik Joaquín Torres-Romero Vincent Nijman David Fernández Timothy M. Eppley 《Global Change Biology》2023,29(20):5775-5787
The world's primates have been severely impacted in diverse and profound ways by anthropogenic pressures. Here, we evaluate the impact of various infrastructures and human-modified landscapes on spatial patterns of primate species richness, at both global and regional scales. We overlaid the International Union for the Conservation of Nature (IUCN) range maps of 520 primate species and applied a global 100 km2 grid. We used structural equation modeling and simultaneous autoregressive models to evaluate direct and indirect effects of six human-altered landscapes variables (i.e., human footprint [HFP], croplands [CROP], road density [ROAD], pasture lands [PAST], protected areas [PAs], and Indigenous Peoples' lands [IPLs]) on global primate species richness, threatened and non-threatened species, as well as on species with decreasing and non-decreasing populations. Two-thirds of all primate species are classified as threatened (i.e., Critically Endangered, Endangered, and Vulnerable), with ~86% experiencing population declines, and ~84% impacted by domestic or international trade. We found that the expansion of PAST, HFP, CROP, and road infrastructure had the most direct negative effects on primate richness. In contrast, forested habitat within IPLs and PAs was positively associated in safeguarding primate species diversity globally, with an even stronger effect at the regional level. Our results show that IPLs and PAs play a critical role in primate species conservation, helping to prevent their extinction; in contrast, HFP growth and expansion has a dramatically negative effect on primate species worldwide. Our findings support predictions that the continued negative impact of anthropogenic pressures on natural habitats may lead to a significant decline in global primate species richness, and likely, species extirpations. We advocate for stronger national and international policy frameworks promoting alternative/sustainable livelihoods and reducing persistent anthropogenic pressures to help mitigate the extinction risk of the world's primate species. 相似文献
107.
Vincent Calcagno Patrice David Philippe Jarne François Massol 《Ecology letters》2023,26(Z1):S140-S151
How the complexity of food webs depends on environmental variables is a long-standing ecological question. It is unclear though how food-chain length should vary with adaptive evolution of the constitutive species. Here we model the evolution of species colonisation rates and its consequences on occupancies and food-chain length in metacommunities. When colonisation rates can evolve, longer food-chains can persist. Extinction, perturbation and habitat loss all affect evolutionarily stable colonisation rates, but the strength of the competition-colonisation trade-off has a major role: weaker trade-offs yield longer chains. Although such eco-evo dynamics partly alleviates the spatial constraint on food-chain length, it is no magic bullet: the highest, most vulnerable, trophic levels are also those that least benefit from evolution. We provide qualitative predictions regarding how trait evolution affects the response of communities to disturbance and habitat loss. This highlights the importance of eco-evolutionary dynamics at metacommunity level in determining food-chain length. 相似文献
108.
Ximena J. Nelson Alex H. Taylor Erica A. Cartmill Heidi Lyn Lauren M. Robinson Vincent Janik Colin Allen 《Biological reviews of the Cambridge Philosophical Society》2023,98(5):1548-1563
The nature and evolution of positive emotion is a major question remaining unanswered in science and philosophy. The study of feelings and emotions in humans and animals is dominated by discussion of affective states that have negative valence. Given the clinical and social significance of negative affect, such as depression, it is unsurprising that these emotions have received more attention from scientists. Compared to negative emotions, such as fear that leads to fleeing or avoidance, positive emotions are less likely to result in specific, identifiable, behaviours being expressed by an animal. This makes it particularly challenging to quantify and study positive affect. However, bursts of intense positive emotion (joy) are more likely to be accompanied by externally visible markers, like vocalisations or movement patterns, which make it more amenable to scientific study and more resilient to concerns about anthropomorphism. We define joy as intense, brief, and event-driven (i.e. a response to something), which permits investigation into how animals react to a variety of situations that would provoke joy in humans. This means that behavioural correlates of joy are measurable, either through newly discovered ‘laughter’ vocalisations, increases in play behaviour, or reactions to cognitive bias tests that can be used across species. There are a range of potential situations that cause joy in humans that have not been studied in other animals, such as whether animals feel joy on sunny days, when they accomplish a difficult feat, or when they are reunited with a familiar companion after a prolonged absence. Observations of species-specific calls and play behaviour can be combined with biometric markers and reactions to ambiguous stimuli in order to enable comparisons of affect between phylogenetically distant taxonomic groups. Identifying positive affect is also important for animal welfare because knowledge of positive emotional states would allow us to monitor animal well-being better. Additionally, measuring if phylogenetically and ecologically distant animals play more, laugh more, or act more optimistically after certain kinds of experiences will also provide insight into the mechanisms underlying the evolution of joy and other positive emotions, and potentially even into the evolution of consciousness. 相似文献
109.
Vincent C. Henrich Leon Livingston Lawrence I. Gilbert 《Genesis (New York, N.Y. : 2000)》1993,14(5):369-377
The ecdysoneless locus in Drosophila melanogaster has been defined previously by a single conditional mutation, I(3)ecd1, that causes an ecdysteroid deficit and larval death at the restrictive temperature, 29°C, although the primary role of the mutation in developmental processes has been unclear. Gene dosage and complementation studies reported here for ecd1 and five nonconditional lethal alleles indicate that the ecd locus plays prezygotic and postzygotic roles essential for normal embryonic development, the successful completion of each larval molt, adult eclosion, and female fertility. The ecd locus is also required for normal macrochaete differentiation. For each observed phenotype, the severity of mutational effects was correlated with ecd mutant genotypes. In all cases, ecd1 homozygotes were least affected. Mutants heteroallelic for ecd1 and any one of four nonconditional recessive mutations were more severely affected than ecd1 homozy-gotes, revealing these as hypomorphic alleles. For all phenotypic effects, mutants heteroallelic for ecd1 and a dominant mutation (ecd3D) were most severely affected. These individuals died during embryogenesis at 29°C and developed no macrochaetes on the dorsal thorax when transferred to 29°C during the white prepupal stage. The ecd3D mutation also caused female semisterility in heterozygotes. Ecdysteroid regulation has been implicated previously in all the developmental processes disrupted by these ecd mutations except for macrochaete differentiation. © 1993 Wiley-Liss, Inc. 相似文献
110.
Aldo Ferretti Vincent P. Flanagan Joseph T. Judd Padmanabhan P. Nair Philip R. Taylor 《The Journal of nutritional biochemistry》1993,4(12)
Dietary supplementation with a fish oil concentrate (FOC) reduced the endogenous synthesis of prostacyclin (PGI2), as measured by the excretion of its major urinary catabolite, 2,3-dinor-6-oxo-PGF1α (PGI2-M). Thirty-four healthy men (24–57 years old) were given controlled diets and supplements that provided 40% of the energy from fat and a minimum of 22 mg/d of α-tocopherol for two consecutive experimental periods of 10 weeks each. During the experimental periods, the men received capsules containing 15 g/d of a placebo oil (PO) (period 1) or 15 g/d of the FOC (period 2). In addition to the PO or FOC, capsules contained 1 mg of α-tocopherol per g of fat as an antioxidant. The average daily excretion of PGI2-M during the last week of FOC supplementation (period 2) was 22% less (P = 0.0001) than at the end of the first period. These results are at variance with those reported in comparable human studies conducted by other investigators during the middle and late 1980s. A 20% reduction (P = 0.003) in the 11-dehydrothromboxane B2 to 2,3-dinor-6-oxo-PGF1α excretion ratio at the end of period 2 in this study demonstrates that a shift of the n-6 to n-3 polyunsaturated fatty acid ratio from 12.5 to 2.3 brings about a substantial modulation of the eicosanoid system. 相似文献