全文获取类型
收费全文 | 3671篇 |
免费 | 279篇 |
国内免费 | 5篇 |
专业分类
3955篇 |
出版年
2023年 | 22篇 |
2022年 | 44篇 |
2021年 | 56篇 |
2020年 | 52篇 |
2019年 | 53篇 |
2018年 | 60篇 |
2017年 | 54篇 |
2016年 | 92篇 |
2015年 | 169篇 |
2014年 | 207篇 |
2013年 | 270篇 |
2012年 | 284篇 |
2011年 | 265篇 |
2010年 | 193篇 |
2009年 | 151篇 |
2008年 | 242篇 |
2007年 | 239篇 |
2006年 | 178篇 |
2005年 | 182篇 |
2004年 | 193篇 |
2003年 | 185篇 |
2002年 | 134篇 |
2001年 | 42篇 |
2000年 | 21篇 |
1999年 | 36篇 |
1998年 | 45篇 |
1997年 | 29篇 |
1996年 | 30篇 |
1995年 | 30篇 |
1994年 | 28篇 |
1993年 | 18篇 |
1992年 | 29篇 |
1991年 | 27篇 |
1990年 | 27篇 |
1989年 | 28篇 |
1988年 | 20篇 |
1987年 | 22篇 |
1986年 | 15篇 |
1985年 | 14篇 |
1984年 | 18篇 |
1983年 | 11篇 |
1982年 | 12篇 |
1981年 | 12篇 |
1980年 | 14篇 |
1978年 | 14篇 |
1976年 | 11篇 |
1975年 | 9篇 |
1974年 | 11篇 |
1973年 | 7篇 |
1967年 | 6篇 |
排序方式: 共有3955条查询结果,搜索用时 0 毫秒
41.
Allison Lange Milo B. Fasken Murray Stewart Anita H. Corbett 《Traffic (Copenhagen, Denmark)》2020,21(10):622-635
The importin α/β transport machinery mediates the nuclear import of cargo proteins that bear a classical nuclear localization sequence (cNLS). These cargo proteins are linked to the major nuclear protein import factor, importin‐β, by the importin‐α adapter, after which cargo/carrier complexes enter the nucleus through nuclear pores. In the nucleus, cargo is released by the action of RanGTP and the nuclear pore protein Nup2, after which the importins are recycled to the cytoplasm for further transport cycles. The nuclear export of importin‐α is mediated by Cse1/CAS. Here, we exploit structures of functionally important complexes to identify residues that are critical for these interactions and provide insight into how cycles of protein import and recycling of importin‐α occur in vivo using a Saccharomyces cerevisiae model. We examine how these molecular interactions impact protein localization, cargo import, function and complex formation. We show that reversing the charge of key residues in importin‐α (Arg44) or Cse1 (Asp220) results in loss of function of the respective proteins and impairs complex formation both in vitro and in vivo. To extend these results, we show that basic residues in the Nup2 N‐terminus are required for both Nup2 interaction with importin‐α and Nup2 function. These results provide a more comprehensive mechanistic model of how Cse1, RanGTP and Nup2 function in concert to mediate cNLS‐cargo release in the nucleus. 相似文献
42.
Lauri Nikkanen Anita Santana Snchez Maria Ermakova Matthias Rgner Laurent Cournac Yagut Allahverdiyeva 《The Plant journal : for cell and molecular biology》2020,103(4):1460-1476
In oxygenic photosynthetic organisms, excluding angiosperms, flavodiiron proteins (FDPs) catalyze light‐dependent reduction of O2 to H2O. This alleviates electron pressure on the photosynthetic apparatus and protects it from photodamage. In Synechocystis sp. PCC 6803, four FDP isoforms function as hetero‐oligomers of Flv1 and Flv3 and/or Flv2 and Flv4. An alternative electron transport pathway mediated by the NAD(P)H dehydrogenase‐like complex (NDH‐1) also contributes to redox hemostasis and the photoprotection of photosynthesis. Four NDH‐1 types have been characterized in cyanobacteria: NDH‐11 and NDH‐12, which function in respiration; and NDH‐13 and NDH‐14, which function in CO2 uptake. All four types are involved in cyclic electron transport. Along with single FDP mutants (?flv1 and Δflv3) and the double NDH‐1 mutants (?d1d2, which is deficient in NDH‐11,2 and ?d3d4, which is deficient in NDH‐13,4), we studied triple mutants lacking one of Flv1 or Flv3, and NDH‐11,2 or NDH‐13,4. We show that the presence of either Flv1/3 or NDH‐11,2, but not NDH‐13,4, is indispensable for survival during changes in growth conditions from high CO2/moderate light to low CO2/high light. Our results show functional redundancy between FDPs and NDH‐11,2 under the studied conditions. We suggest that ferredoxin probably functions as a primary electron donor to both Flv1/3 and NDH‐11,2, allowing their functions to be dynamically coordinated for efficient oxidation of photosystem I and for photoprotection under variable CO2 and light availability. 相似文献
43.
Lucy E. Ridding Adrian C. Newton Sally A. Keith Robin M. Walls Anita Diaz Richard F. Pywell James M. Bullock 《Ecography》2021,44(1):33-43
The extinction debt, delayed species extinctions following landscape degradation, is a widely discussed concept. But a consensus about the prevalence of extinctions debts is hindered by a multiplicity of methods and a lack of comparisons among habitats. We applied three contrasting species–area relationship methods to test for plant community extinction debts in three habitats which had different degradation histories over the last century: calcareous grassland, heathland and woodland. These methods differ in their data requirements, with the first two using information on past and current habitat area alongside current species richness, whilst the last method also requires data on past species richness. The most data‐intensive, and hence arguably most reliable method, identified extinction debts across all habitats for specialist species, whilst the other methods did not. All methods detected an extinction debt in calcareous grassland, which had undergone the most severe degradation. We conclude that some methods failed to detect an extinction debt, particularly in habitats that have undergone moderate degradation. Data on past species numbers are required for the most reliable method; as such data are rare, extinction debts may be under‐reported. 相似文献
44.
Amino Acids - Solid-phase synthesis of cyclic, branched or side-chain-modified peptides typically involves introduction of a residue carrying a temporary side-chain protecting group that undergoes... 相似文献
45.
Charles A. Krauth Anita T. Shortnacy John K Montgomery John A. Secrist III 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):915-917
Abstract The antiviral activity of adenosine-N1-oxide (1) and a variety of substituted 1-(benzyloxy) adenosines (2) has been re-investigated and significant in vitro activity vs. Vaccinia virus has been shown. In vivo activity in mice has also been demonstrated. 相似文献
46.
Anita K. Gandhi Tao Shi Mingyu Li Ulf Jungnelius Alfredo Romano Josep Tabernero Salvatore Siena Peter H. Schafer Rajesh Chopra 《PloS one》2013,8(11)
This study assessed the immunomodulatory effects in previously treated KRAS-mutant metastatic colorectal cancer patients participating in a phase II multicenter, open-label clinical trial receiving lenalidomide alone or lenalidomide plus cetuximab. The main findings show the T cell immunostimulatory properties of lenalidomide as the drug induced a decrease in the percentage CD45RA+ naïve T cells 3-fold while increasing the percentage HLA-DR+ activated T helper cells and percentage total CD45RO+ CD8+ memory T cytotoxic cells, 2.6- and 2.1-fold respectively (p<0.0001). In addition, lenalidomide decreased the percentage of circulating CD19+ B cells 2.6-fold (p<0.0001). Lenalidomide increased a modest, yet significant, 1.4-fold change in the percentage of circulating natural killer cells. Our findings indicate that lenalidomide significantly activates T cells, suggestive of an immunotherapeutic role for this drug in settings of maintenance therapy and tumor immunity. Furthermore, reported for the first time is the effect of lenalidomide in combination with cetuximab on T cell function, including increases in circulating naïve and central memory T cells. In summary, lenalidomide and cetuximab have significant effects on circulating immune cells in patients with colorectal carcinoma.
Trial Registration
ClinicalTrials.gov NCT01032291相似文献47.
Carla M. Zammit Davide Quaranta Shane Gibson Anita J. Zaitouna Christine Ta Jo?l Brugger Rebecca Y. Lai Gregor Grass Frank Reith 《PloS one》2013,8(8)
Geochemical exploration for gold (Au) is becoming increasingly important to the mining industry. Current processes for Au analyses require sampling materials to be taken from often remote localities. Samples are then transported to a laboratory equipped with suitable analytical facilities, such as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) or Instrumental Neutron Activation Analysis (INAA). Determining the concentration of Au in samples may take several weeks, leading to long delays in exploration campaigns. Hence, a method for the on-site analysis of Au, such as a biosensor, will greatly benefit the exploration industry. The golTSB genes from Salmonella enterica serovar typhimurium are selectively induced by Au(I/III)-complexes. In the present study, the golTSB operon with a reporter gene, lacZ, was introduced into Escherichia coli. The induction of golTSB::lacZ with Au(I/III)-complexes was tested using a colorimetric β-galactosidase and an electrochemical assay. Measurements of the β-galactosidase activity for concentrations of both Au(I)- and Au(III)-complexes ranging from 0.1 to 5 µM (equivalent to 20 to 1000 ng g−1 or parts-per-billion (ppb)) were accurately quantified. When testing the ability of the biosensor to detect Au(I/III)-complexes(aq) in the presence of other metal ions (Ag(I), Cu(II), Fe(III), Ni(II), Co(II), Zn, As(III), Pb(II), Sb(III) or Bi(III)), cross-reactivity was observed, i.e. the amount of Au measured was either under- or over-estimated. To assess if the biosensor would work with natural samples, soils with different physiochemical properties were spiked with Au-complexes. Subsequently, a selective extraction using 1 M thiosulfate was applied to extract the Au. The results showed that Au could be measured in these extracts with the same accuracy as ICP-MS (P<0.05). This demonstrates that by combining selective extraction with the biosensor system the concentration of Au can be accurately measured, down to a quantification limit of 20 ppb (0.1 µM) and a detection limit of 2 ppb (0.01 µM). 相似文献
48.
Nives ?kunca Matko Bo?njak Anita Kri?ko Pan?e Panov Sa?o D?eroski Tomislav ?muc Fran Supek 《PLoS computational biology》2013,9(1)
New microbial genomes are sequenced at a high pace, allowing insight into the genetics of not only cultured microbes, but a wide range of metagenomic collections such as the human microbiome. To understand the deluge of genomic data we face, computational approaches for gene functional annotation are invaluable. We introduce a novel model for computational annotation that refines two established concepts: annotation based on homology and annotation based on phyletic profiling. The phyletic profiling-based model that includes both inferred orthologs and paralogs—homologs separated by a speciation and a duplication event, respectively—provides more annotations at the same average Precision than the model that includes only inferred orthologs. For experimental validation, we selected 38 poorly annotated Escherichia coli genes for which the model assigned one of three GO terms with high confidence: involvement in DNA repair, protein translation, or cell wall synthesis. Results of antibiotic stress survival assays on E. coli knockout mutants showed high agreement with our model''s estimates of accuracy: out of 38 predictions obtained at the reported Precision of 60%, we confirmed 25 predictions, indicating that our confidence estimates can be used to make informed decisions on experimental validation. Our work will contribute to making experimental validation of computational predictions more approachable, both in cost and time. Our predictions for 998 prokaryotic genomes include ∼400000 specific annotations with the estimated Precision of 90%, ∼19000 of which are highly specific—e.g. “penicillin binding,” “tRNA aminoacylation for protein translation,” or “pathogenesis”—and are freely available at http://gorbi.irb.hr/. 相似文献
49.
S. K. Sood B. Vijay Simha Rashmi Kumariya Anita Kumari Garsa Jitender Mehla Sunita Meena Puja Lather 《Probiotics and antimicrobial proteins》2013,5(1):37-42
A novel method based on (1) initial microbiological screening and (2) a highly specific PCR is described for selection of strains expressing YGNGV motif-containing pediocin. Initial screening is carried out using spot on the lawn assay for selection of acid-free, hydrogen peroxide (H2O2)-free and secreted heat-stable inhibitory activity producing strains. This is followed by highly specific PCR for amplification of 406-bp fragment using forward primer: 5′-tggccaatatcattggtggt-3′ targeting signal peptide sequence of pediocin structural gene and reverse primer: 5′-ctactaacgcttggctggca-3′ encoding N-terminus of immunity gene. The assay was validated with Pediococcus pentosaceus NCDC273 and Pediococcus acidilactici NCDC252 using (1) digestion of amplified 406-bp fragment with HindIII restriction enzyme-producing two restriction fragments of expected sizes (227 and 179 bp), (2) nucleotide sequencing of 406-bp fragment from both strains found these pediocins identical to pediocin PA-1/AcH and (3) identification of both pediocins as pediocin PA-1 at protein level using RP-HPLC. The assay was used for screening six strains (3 pediococci, 2 lactobacilli and an Enterococcus faecium) producing acid-free, hydrogen peroxide (H2O2)-free and secreted heat-stable inhibitory activity. This resulted in the detection of three new strains (P. pentosaceus NCDC35, E. faecium NCDC124 and Lactobacillus plantarum NCDC20) producing YGNGV motif-containing pediocins. 相似文献
50.
Culture, Medicine, and Psychiatry - In this article, we explore the power of shared embodiment for the constitution of an affective community. More specifically, we examine how people afflicted by... 相似文献