全文获取类型
收费全文 | 2986篇 |
免费 | 202篇 |
专业分类
3188篇 |
出版年
2022年 | 28篇 |
2021年 | 27篇 |
2020年 | 24篇 |
2019年 | 40篇 |
2018年 | 39篇 |
2017年 | 50篇 |
2016年 | 55篇 |
2015年 | 109篇 |
2014年 | 107篇 |
2013年 | 186篇 |
2012年 | 217篇 |
2011年 | 178篇 |
2010年 | 136篇 |
2009年 | 117篇 |
2008年 | 207篇 |
2007年 | 232篇 |
2006年 | 198篇 |
2005年 | 179篇 |
2004年 | 192篇 |
2003年 | 183篇 |
2002年 | 184篇 |
2001年 | 41篇 |
2000年 | 37篇 |
1999年 | 30篇 |
1998年 | 31篇 |
1997年 | 22篇 |
1996年 | 26篇 |
1995年 | 24篇 |
1994年 | 33篇 |
1993年 | 24篇 |
1992年 | 16篇 |
1991年 | 19篇 |
1990年 | 15篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 20篇 |
1986年 | 14篇 |
1985年 | 12篇 |
1984年 | 20篇 |
1983年 | 13篇 |
1982年 | 12篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 6篇 |
1972年 | 7篇 |
1971年 | 5篇 |
1969年 | 3篇 |
排序方式: 共有3188条查询结果,搜索用时 46 毫秒
41.
Takimoto Yuki Monkawa Akira Nagata Kohki Kobayashi Masahiro Kinoshita Mariko Gessei Tomoko Mori Toshiya Kagi Hiroyuki 《Plasmonics (Norwell, Mass.)》2020,15(3):805-811
Plasmonics - Detection and monitoring of SO2 is important because it is a representative toxic gas in the atmospheric environment that is emitted from industrial and natural processes. Localized... 相似文献
42.
Sequence Analysis of Amplified DNA Fragments Containing the Region Encoding the Putative Lipase Substrate-Binding Domain and Genotyping of Aeromonas hydrophila 下载免费PDF全文
Noboru Watanabe Koji Morita Tomoko Furukawa Taki Manzoku Eiko Endo Masato Kanamori 《Applied microbiology》2004,70(1):145-151
DNA fragments were amplified by PCR from all tested strains of Aeromonas hydrophila, A. caviae, and A. sobria with primers designed based on sequence alignment of all lipase, phospholipase C, and phospholipase A1 genes and the cytotonic enterotoxin gene, all of which have been reported to have the consensus region of the putative lipase substrate-binding domain. All strains showed lipase activity, and all amplified DNA fragments contained a nucleotide sequence corresponding to the substrate-binding domain. Thirty-five distinct nucleotide sequence patterns and 15 distinct deduced amino acid sequence patterns were found in the amplified DNA fragments from 59 A. hydrophila strains. The deduced amino acid sequences of the amplified DNA fragments from A. caviae and A. sobria strains had distinctive amino acids, suggesting a species-specific sequence in each organism. Furthermore, the amino acid sequence patterns appear to differ between clinical and environmental isolates among A. hydrophila strains. Some strains whose nucleotide sequences were identical to one another in the amplified region showed an identical DNA fingerprinting pattern by repetitive extragenic palindromic sequence-PCR genotyping. These results suggest that A. hydrophila, and also A. caviae and A. sobria strains, have a gene encoding a protein with lipase activity. Homologs of the gene appear to be widely distributed in Aeromonas strains, probably associating with the evolutionary genetic difference between clinical and environmental isolates of A. hydrophila. Additionally, the distinctive nucleotide sequences of the genes could be attributed to the genotype of each strain, suggesting that their analysis may be helpful in elucidating the genetic heterogeneity of Aeromonas. 相似文献
43.
Tumor suppressor in lung cancer (TSLC)1 suppresses epithelial cell scattering and tubulogenesis 总被引:3,自引:0,他引:3
Masuda M Kikuchi S Maruyama T Sakurai-Yageta M Williams YN Ghosh HP Murakami Y 《The Journal of biological chemistry》2005,280(51):42164-42171
The tumor suppressor in lung cancer 1 (TSLC1/IGSF4) encodes an immunoglobulin-superfamily cell adhesion molecule whose cytoplasmic domain contains a protein 4.1-binding motif (protein 4.1-BM) and a PDZ-binding motif (PDZ-BM). Loss of TSLC1 expression is frequently observed in advanced cancers implying its involvement in tumor invasion and/or metastasis. Using Madin-Darby canine kidney cells expressing a full-length TSLC1 or various cytoplasmic deletion mutants of TSLC1, we examined the role of TSLC1 in epithelial mesenchymal transitions during the hepatocyte growth factor (HGF)-induced tubulogenesis and cell scattering. In a three-dimensional culture, the full-length TSLC1, which was localized to the lateral membrane of Madin-Darby canine kidney cysts, inhibited HGF-induced tubulogenesis. In contrast, the mutants lacking either the protein 4.1-BM or the PDZ-BM abolished the inhibitory effect on tubulogenesis. In addition, these mutants showed aberrant subcellular localization indicating that lateral localization is correlated with the effect of TSLC1. In a two-dimensional culture, the full-length TSLC1, but not the mutants lacking the protein 4.1-BM or the PDZ-BM, suppressed HGF-induced cell scattering. Furthermore, the cells expressing full-length TSLC1 retained E-cadherin-based cell-cell adhesion even after being treated with HGF. These cells showed prolonged activation of Rac and low activity of Rho, whereas the HGF-treated parental cells induced transient activation of Rac and sustained activation of Rho. Prolonged Rac activation caused by the expression of TSLC1 required its cytoplasmic tail. These findings, taken together, suggest that TSLC1 plays a role in suppressing induction of epithelial mesenchymal transitions by regulating the activation of small Rho GTPases. 相似文献
44.
Koshikawa N Minegishi T Sharabi A Quaranta V Seiki M 《The Journal of biological chemistry》2005,280(1):88-93
Processing of the laminin-5 (Ln-5) gamma 2 chain by membrane-type-1 matrix metalloproteinases (MT1-MMP) promotes migration and invasion of epithelial and tumor cells. We previously demonstrated that MT1-MMP cleaves the rat gamma 2 chain at two sites, producing two major C-terminal fragments of 100 (gamma 2') and 80 (gamma 2 x) kDa and releasing a 30-kDa fragment containing epidermal growth factor (EGF)-like motifs (domain III (DIII) fragment). The DIII fragment bound the EGF receptor (EGF-R) and stimulated cell scattering and migration. However, it is not yet clear whether human Ln-5 is processed in a similar fashion to rat Ln-5 because one of the two MT1-MMP cleavage sites present in rat gamma 2 is not found in human gamma 2. To identify the exact cleavage site for MT1-MMP in human Ln-5, we purified both the whole molecule as well as a monomeric form of human gamma 2 that is frequently expressed by malignant tumor cells. Like rat Ln-5, both the monomer of gamma 2, as well as the gamma 2 derived from intact Ln-5, were cleaved by MT1-MMP in vitro, generating C-terminal gamma 2' (100 kDa) and gamma 2 x (85 kDa) fragments and releasing DIII fragments (25 and 27k Da). In addition to the conserved first cleavage site used to generate gamma 2', two adjacent cleavage sites (Gly(559)-Asp(560) and Gly(579)-Ser(580)) were found that could generate the gamma 2 x and DIII fragments. Two of the three EGF-like motifs present in the rat DIII fragment are present in the 27-kDa human fragment, and like the rat DIII, this fragment can promote breast carcinoma cell migration by engaging the EGF-R. These results suggest that MT1-MMP processing of Ln-5 in human tumors may stimulate the EGF-R, resulting in increased tumor cell scattering and migration that could possibly increase their metastatic potential. 相似文献
45.
Asaki T Sugiyama Y Hamamoto T Higashioka M Umehara M Naito H Niwa T 《Bioorganic & medicinal chemistry letters》2006,16(5):1421-1425
A series of 3-substituted benzamide derivatives structurally related to STI-571 (imatinib mesylate), a Bcr-Abl tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML), was prepared and evaluated for antiproliferative activity against the Bcr-Abl-positive leukemia cell line K562. About ten 3-halogenated and 3-trifluoromethylated benzamide derivatives were identified as highly potent Bcr-Abl kinase inhibitors. One of these, NS-187 (9b), is a promising new candidate Bcr-Abl inhibitor for the therapy of STI-571-resistant chronic myeloid leukemia. 相似文献
46.
47.
Yamada H Tamada T Kosaka M Miyata K Fujiki S Tano M Moriya M Yamanishi M Honjo E Tada H Ino T Yamaguchi H Futami J Seno M Nomoto T Hirata T Yoshimura M Kuroki R 《Protein science : a publication of the Protein Society》2007,16(7):1389-1397
A protein crystal lattice consists of surface contact regions, where the interactions of specific groups play a key role in stabilizing the regular arrangement of the protein molecules. In an attempt to control protein incorporation in a crystal lattice, a leucine zipper-like hydrophobic interface (comprising four leucine residues) was introduced into a helical region (helix 2) of the human pancreatic ribonuclease 1 (RNase 1) that was predicted to form a suitable crystallization interface. Although crystallization of wild-type RNase 1 has not yet been reported, the RNase 1 mutant having four leucines (4L-RNase 1) was successfully crystallized under several different conditions. The crystal structures were subsequently determined by X-ray crystallography by molecular replacement using the structure of bovine RNase A. The overall structure of 4L-RNase 1 is quite similar to that of the bovine RNase A, and the introduced leucine residues formed the designed crystal interface. To characterize the role of the introduced leucine residues in crystallization of RNase 1 further, the number of leucines was reduced to three or two (3L- and 2L-RNase 1, respectively). Both mutants crystallized and a similar hydrophobic interface as in 4L-RNase 1 was observed. A related approach to engineer crystal contacts at helix 3 of RNase 1 (N4L-RNase 1) was also evaluated. N4L-RNase 1 also successfully crystallized and formed the expected hydrophobic packing interface. These results suggest that appropriate introduction of a leucine zipper-like hydrophobic interface can promote intermolecular symmetry for more efficient protein crystallization in crystal lattice engineering efforts. 相似文献
48.
Kimura KR Nakata M Sumitomo T Kreikemeyer B Podbielski A Terao Y Kawabata S 《Journal of bacteriology》2012,194(4):804-812
The group A streptococcus (GAS) Streptococcus pyogenes is known to cause self-limiting purulent infections in humans. The role of GAS pili in host cell adhesion and biofilm formation is likely fundamental in early colonization. Pilus genes are found in the FCT (fibronectin-binding protein, collagen-binding protein, and trypsin-resistant antigen) genomic region, which has been classified into nine subtypes based on the diversity of gene content and nucleotide sequence. Several epidemiological studies have indicated that FCT type 1 strains, including serotype M6, produce large amounts of monospecies biofilm in vitro. We examined the direct involvement of pili in biofilm formation by serotype M6 clinical isolates. In the majority of tested strains, deletion of the tee6 gene encoding pilus shaft protein T6 compromised the ability to form biofilm on an abiotic surface. Deletion of the fctX and srtB genes, which encode pilus ancillary protein and class C pilus-associated sortase, respectively, also decreased biofilm formation by a representative strain. Unexpectedly, these mutant strains showed increased bacterial aggregation compared with that of the wild-type strain. When the entire FCT type 1 pilus region was ectopically expressed in serotype M1 strain SF370, biofilm formation was promoted and autoaggregation was inhibited. These findings indicate that assembled FCT type 1 pili contribute to biofilm formation and also function as attenuators of bacterial aggregation. Taken together, our results show the potential role of FCT type 1 pili in the pathogenesis of GAS infections. 相似文献
49.
50.
Abe M Sogabe Y Syuto T Yokoyama Y Ishikawa O 《Journal of cellular biochemistry》2007,102(5):1290-1299
Fibroblast-collagen matrix contraction has been used as a model system to study how cells organize connective tissue. Previous work showed that lysophosphatidic acid (LPA)-stimulated floating collagen matrix contraction is independent of Rho kinase while platelet-derived growth factor (PDGF)-stimulated contraction is Rho kinase-dependent. The current studies were carried out to determine the signaling mechanisms of basic fibroblast growth factor (bFGF)-stimulated fibroblast-collagen matrix contraction. Both bFGF and LPA promoted equally collagen matrix contraction well. Three different inhibitors, LY294002 for phosphatidylinositol-3-kinase (PI3K), C3 exotransferase for Rho and Y27632 for Rho kinase, suppressed the bFGF-stimulated fibroblast-collagen matrix contraction. With bFGF stimulation, fibroblasts spread with prominent stress fiber network formation and focal adhesions. In the presence of Rho kinase inhibitor, focal adhesions and stress fibers were mostly lost. We demonstrated that bFGF stimulation for fibroblast caused transient Rac and Rho activation but did not activate Cdc42. In addition, bFGF enhanced fibroblast migration in wound healing assay. The present study implicates PI3K, Rac, Rho, and Rho kinase as being involved in bFGF-stimulated collagen matrix contraction. The elucidation of bFGF-triggered signal transduction may be an important clue to understand the roles of bFGF in wound healing. 相似文献