全文获取类型
收费全文 | 1506篇 |
免费 | 140篇 |
国内免费 | 77篇 |
出版年
2024年 | 4篇 |
2023年 | 13篇 |
2022年 | 30篇 |
2021年 | 27篇 |
2020年 | 35篇 |
2019年 | 37篇 |
2018年 | 35篇 |
2017年 | 33篇 |
2016年 | 35篇 |
2015年 | 41篇 |
2014年 | 104篇 |
2013年 | 134篇 |
2012年 | 100篇 |
2011年 | 84篇 |
2010年 | 55篇 |
2009年 | 107篇 |
2008年 | 118篇 |
2007年 | 85篇 |
2006年 | 85篇 |
2005年 | 94篇 |
2004年 | 78篇 |
2003年 | 44篇 |
2002年 | 42篇 |
2001年 | 34篇 |
2000年 | 27篇 |
1999年 | 20篇 |
1998年 | 31篇 |
1997年 | 47篇 |
1996年 | 30篇 |
1995年 | 45篇 |
1994年 | 14篇 |
1993年 | 21篇 |
1992年 | 10篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1976年 | 1篇 |
排序方式: 共有1723条查询结果,搜索用时 957 毫秒
1.
Benjamin C. Blum Weiwei Lin Matthew L. Lawton Qian Liu Julian Kwan Isabella Turcinovic Ryan Hekman Pingzhao Hu Andrew Emili 《Molecular & cellular proteomics : MCP》2022,21(1):100189
Metabolism is recognized as an important driver of cancer progression and other complex diseases, but global metabolite profiling remains a challenge. Protein expression profiling is often a poor proxy since existing pathway enrichment models provide an incomplete mapping between the proteome and metabolism. To overcome these gaps, we introduce multiomic metabolic enrichment network analysis (MOMENTA), an integrative multiomic data analysis framework for more accurately deducing metabolic pathway changes from proteomics data alone in a gene set analysis context by leveraging protein interaction networks to extend annotated metabolic models. We apply MOMENTA to proteomic data from diverse cancer cell lines and human tumors to demonstrate its utility at revealing variation in metabolic pathway activity across cancer types, which we verify using independent metabolomics measurements. The novel metabolic networks we uncover in breast cancer and other tumors are linked to clinical outcomes, underscoring the pathophysiological relevance of the findings. 相似文献
2.
Y. Saijo S. Takeda A. Scherer T. Kobayashi Y. Mada H. Taniguchi M. Yao S. Wakatsuki 《Protein science : a publication of the Protein Society》1997,6(4):916-918
Troponin is a ternary protein complex consisting of subunits TnC. TnI, and TnT, and plays a key role in calcium regulation of the skeletal and cardiac muscle contraction. In the present study, a partial complex (CI47) was prepared from Escherichia coli-expressed rabbit skeletal muscle TnC and fragment 1-47 of TnI, which is obtained by chemical cleavage of an E. coli-expressed mutant of rabbit skeletal muscle TnI. Within the ternary troponin complex, CI47 is thought to form a core that is resistant to proteolytic digestion, and the interaction within CI47 likely maintains the integrity of the troponin complex. Complex CI47 was crystallized in the presence of sodium citrate. The addition of trehalose improved the diffraction pattern of the crystals substantially. The crystal lattice belongs to the space group P3(1)(2)21, with unit cell dimensions a = b = 48.2 A, c = 162 A. The asymmetric unit presumably contains one CI47 complex. Soaking with p-chloromercuribenzenesulfonate (PCMBS) resulted in loss of isomorphism, but enhanced the quality of the crystals. The crystals diffracted up to 2.3 A resolution, with completeness of 91% and R(merge) = 6.4%. The crystals of PCMBS-derivative should be suitable for X-ray studies using the multiple-wavelength anomalous diffraction technique. This is the first step for elucidating the structure of the full troponin complex. 相似文献
3.
《Molecular & cellular proteomics : MCP》2023,22(2):100490
Aspergillus flavus is a common saprophytic and pathogenic fungus, and its secondary metabolic pathways are one of the most highly characterized owing to its aflatoxin (AF) metabolite affecting global economic crops and human health. Different natural environments can cause significant variations in AF synthesis. Succinylation was recently identified as one of the most critical regulatory post-translational modifications affecting metabolic pathways. It is primarily reported in human cells and bacteria with few studies on fungi. Proteomic quantification of lysine succinylation (Ksuc) exploring its potential involvement in secondary metabolism regulation (including AF production) has not been performed under natural conditions in A. flavus. In this study, a quantification method was performed based on tandem mass tag labeling and antibody-based affinity enrichment of succinylated peptides via high accuracy nano-liquid chromatography with tandem mass spectrometry to explore the succinylation mechanism affecting the pathogenicity of naturally isolated A. flavus strains with varying toxin production. Altogether, 1240 Ksuc sites in 768 proteins were identified with 1103 sites in 685 proteins quantified. Comparing succinylated protein levels between high and low AF-producing A. flavus strains, bioinformatics analysis indicated that most succinylated proteins located in the AF biosynthetic pathway were downregulated, which directly affected AF synthesis. Versicolorin B synthase is a key catalytic enzyme for heterochrome B synthesis during AF synthesis. Site-directed mutagenesis and biochemical studies revealed that versicolorin B synthase succinylation is an important regulatory mechanism affecting sclerotia development and AF biosynthesis in A. flavus. In summary, our quantitative study of the lysine succinylome in high/low AF-producing strains revealed the role of Ksuc in regulating AF biosynthesis. We revealed novel insights into the metabolism of AF biosynthesis using naturally isolated A. flavus strains and identified a rich source of metabolism-related enzymes regulated by succinylation. 相似文献
4.
为了验证转基因烟草中表达的外壳蛋白(CP)能够重新包被侵入的烟草花叶病毒(TMV)的假设,利用抗原表位标记的方法观察CP亚单位在病毒5′端的交换。通过PCR 方法将来源于鼠肝炎病毒(MHV) S蛋白的两个小肽段(11 a.a.和15 a.a.)的DNA序列分别插入TMV-U1 CP基因邻近3′端的两个位点,并构建了带有外源序列的TMV 侵染克隆V9 (11 a.a.)和E15 (15 a.a.)。通过体外转录反应,得到V9 RNA 及E15 RNA。突变病毒RNA 侵染烟草(Nicotiana tabacum )后表现不同特性。V9 和E15 侵染XanthiNN烟草后同野生型TMV一样产生枯斑。但是,当它们侵染Xanthinn 烟草时,V9 产生同侵染XanthiNN 烟草相同的枯斑,而E15的特性同TMV-U1几乎完全相同,能对Xanthinn 烟草进行系统侵染并在叶片中聚集大量的带有外源片段的外壳蛋白,而且病毒的结构极其稳定。V9 和E15 特性的差异可能是由于外源片段在外壳蛋白中存在位置的不同影响了外壳蛋白的结构所致 相似文献
5.
The lactose permease is being used as a model system for the rational redesign of a membrane protein with the goal of increasing the likelihood of crystallization. Various modifications to the protein have been added for the purposes of purification, stability, and potential for crystallization. The addition of six consecutive histidines at the C-terminus of the protein allows for the rapid purification by nickel-chelate chromatography, and the insertion of an entire protein domain into one of the inner cytoplasmic loops of the permease gives the resulting protein a larger hydrophilic surface area. The increase in polar surface area makes the fusion protein easier to handle and more likely to crystallize. In particular, the introduction of cytochromeb562 ofE. coli into the central hydrophilic domain of the lac permease results in a fusion protein with the transport activity of the permease and the visible absorbance spectrum of the cytochrome. The red permease is very easy to monitor through the steps of expression, purification, concentration, and crystallization. 相似文献
6.
Abstract: Endangered Hawaiian monk seal ( Monachs schauinslandi ) pups at all the major breeding islands in the Northwestern Hawaiian Islands have been tagged since the early 1980s. Pups were double flipper tagged as soon as possible post-weaning. With few exceptions, an extensive tag resighting effort was conducted annually at the same islands. These resighting data were used to estimate seal survival rates from the time of tagging to age one at all locations using the ratio of seals alive in the second year to number of pups tagged. These survival rates among the islands, from weaning to age one, averaged over the years of the study, ranged from 0.80 to 0.90. For young seals over age one, capture-recapture methods were used to calculate survival pooled through several years, and these rates ranged from 0.85 to 0.98. At French Frigate Shoals and Laysan Island, the higher numbers of tagged pups allowed separate estimates of male and female survival to be calculated. These rates suggested that survival of immature females was better than males. Beginning in 1989, survival of immature seals at French Frigate Shoals declined sharply. 相似文献
7.
Michael Kokkinidis Metaxia Vlassi Yannis Papanikolaou Dina Kotsifaki Adrian Kingswell Demetrius Tsernoglou Hans-Juuml;rgen Hinz 《Proteins》1993,16(2):214-216
Six variants of the ROP protein, designed with the aim to analyze by X-ray crystallography loop formation and core packing interactions in 4-α-helical bundles- have been purified and a search of their crystallization conditions has been carried out. Five mutants yield crystals that are suitable for medium to high resolutionX-ray diffraction studies. For all mutants crystal size- sensitivity to X-irradiation and diffraction limit are correlated to their stability as determined by differential scanning calorimetry- in a manner which is not yet understood in detail. © Wiley-Liss, Inc. 相似文献
8.
Cathleen A. Earhart G. Sridhar Prasad Debra L. Murray Richard P. Novick Patrick M. Schlievert Douglas H. Ohlendorf 《Proteins》1993,17(3):329-334
Native toxic shock syndrom toxin 1 (TSST-1) purified from Staphylococcus aurius has been crystallized in four different forms. The highest resolution data (2.05 Å) was collected from orthorhombic crystals belonging to the space group C2221. The unit cell dimension are a = 108.7 Å, b = 177.5 Å, c = 97.6 Å. Rotation function analysis of this from indicates that there is trimer of toxin molecules in the asymmetric unit with a local 3-fold axis parallel to the crystallographic c axis. Crystals of a double mutant of TSST-1 have been grown which has a single molecule in the asymmetric unit and diffract to 1.9 Å. The space group is P21 with unit cell parameters of a = 44.4 Å, b = 34.0 Å, c = 55.2 Å, β = 93.0°. © 1993 Wiley-Liss, Inc. 相似文献
9.
Single crystals were grown from affinity-purified stinging nettle lectin and from its complex with the specific trisaccharide NN′N″ -triacetylchitotriose by vapor diffusion at room temperature. The lectin crystallizes in space group P212121 with unit cell dimensions a = 54.3 (1) Å, b = 62.2 (1) Å, and c = 92.4 (2) Å, and diffracts to 3.0 Å resolution. The asymmetric unit contains three lectin monomers. The crystals of the lectin-trisaccharide complex have space group P212121 with cell constants a = 37.69 (4) Å, b = 48.97 (6) Å, and c = 57.32 (4) Å. These crystals diffract to at least 2.0 Å resolution and the asymmetric unit contains one lectin monomer. A three-dimensional X-ray structure determination is on its way. © 1993 Wiley-Liss, Inc. 相似文献
10.
Yoko Ino Yutaro Yamaoka Kiho Tanaka Kei Miyakawa Mayuko Nishi Yasuyoshi Hatayama Hirokazu Kimura Yayoi Kimura Akihide Ryo 《Proteomics》2023,23(11):2200334
Peptide tag systems are a robust biophysical and biochemical method that is widely used for protein detection and purification. Here, we developed a novel tag system termed “HiP4” (histidine plus four amino acids) whose epitope sequence comprises only seven amino acids (HHHDYDI) that partially overlap with the conventional 6x histidine tag (6xHis-tag). We produced a monoclonal antibody against the HiP4 tag that can be used in multiple immunoassays with high specificity and affinity. Using this system, we developed a tandem affinity purification (TAP) and mass spectrometry (TAP-MS) system for comprehensive protein interactome analysis. The integrated use of nickel bead purification followed by HiP4 tag immunoprecipitation made it possible to reduce nonspecific binding and improve selectivity, leading to the recovery of previously unrecognized proteins that interact with hepatitis B virus X (HBx) protein or TAR DNA-binding protein 43 (TARDBP or TDP-43). Our results indicate that this system may be viable as a simple and powerful tool for TAP-MS that can achieve low background and high selectivity in comprehensive protein–protein interaction analyses. 相似文献