全文获取类型
收费全文 | 56290篇 |
免费 | 4707篇 |
国内免费 | 49篇 |
专业分类
61046篇 |
出版年
2023年 | 200篇 |
2022年 | 584篇 |
2021年 | 1003篇 |
2020年 | 556篇 |
2019年 | 741篇 |
2018年 | 1133篇 |
2017年 | 889篇 |
2016年 | 1569篇 |
2015年 | 2585篇 |
2014年 | 2876篇 |
2013年 | 3370篇 |
2012年 | 4352篇 |
2011年 | 4167篇 |
2010年 | 2643篇 |
2009年 | 2320篇 |
2008年 | 3339篇 |
2007年 | 3101篇 |
2006年 | 2835篇 |
2005年 | 2559篇 |
2004年 | 2503篇 |
2003年 | 2227篇 |
2002年 | 1898篇 |
2001年 | 1645篇 |
2000年 | 1536篇 |
1999年 | 1218篇 |
1998年 | 528篇 |
1997年 | 468篇 |
1996年 | 401篇 |
1995年 | 393篇 |
1994年 | 305篇 |
1993年 | 298篇 |
1992年 | 639篇 |
1991年 | 515篇 |
1990年 | 474篇 |
1989年 | 479篇 |
1988年 | 405篇 |
1987年 | 390篇 |
1986年 | 318篇 |
1985年 | 329篇 |
1984年 | 270篇 |
1983年 | 224篇 |
1982年 | 189篇 |
1981年 | 162篇 |
1980年 | 160篇 |
1979年 | 220篇 |
1978年 | 197篇 |
1977年 | 179篇 |
1976年 | 170篇 |
1974年 | 196篇 |
1972年 | 155篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
A closed-loop artificial pancreas based on model predictive control: Human-friendly identification and automatic meal disturbance rejection 总被引:1,自引:0,他引:1
Type 1 diabetes is characterized by a lack of insulin production by the pancreas, causing high blood glucose concentrations and requiring external insulin infusion to regulate blood glucose. Continuous glucose sensors can be coupled with continuous insulin infusion pumps to create a closed-loop artificial pancreas. A novel procedure of “human-friendly” identification testing using multisine inputs is developed to estimate suitable models for use in an artificial pancreas. A constrained model predictive control (MPC) strategy is developed to reduce risks of hypo- and hyperglycemia (low and high blood glucose concentration). Meal detection and meal size estimation algorithms are developed to improve meal glucose disturbance rejection when incoming meals are not announced. Closed-loop performance is evaluated through simulation studies of a type 1 diabetic individual, illustrating the ability of the MPC-based artificial pancreas control strategy to handle announced and unannounced meal disturbances. 相似文献
992.
Changhyun Lee Jaeyoung Chun Sung Wook Hwang Seung Joo Kang Jong Pil Im Joo Sung Kim 《Life sciences》2014
Aims
Intestinal alkaline phosphatase (IAP) is an intestinal brush border enzyme that is shown to function as a gut mucosal defense factor, but its defensive mechanism remains unclear. The aims of this study were to evaluate the effect of IAP on intestinal epithelial cells and macrophages, and on chronic colitis in interleukin-10-deficient (IL-10−/−) mice.Main methods
Human intestinal epithelial cells COLO 205 and peritoneal macrophages from IL-10−/− mice were pretreated with IAP and then stimulated with lipopolysaccharide (LPS). IL-8 secretion from COLO205 cells and TNF-α, IL-6, IL-12 from peritoneal macrophages were measured by ELISA. Electrophoretic mobility shift assay was used to assess the DNA binding activity of NF-κB and IκBα phosphorylation/degradation was evaluated by immunoblot assay in COLO 205. For the in vivo study, colitis was induced in IL-10−/− mice with piroxicam, the mice were then treated with 100 or 300 units of IAP by oral gavage for 2 weeks. Colitis was quantified by histopathologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry.Key findings
IAP significantly inhibited LPS-induced inflammatory cytokine production in both IECs and peritoneal macrophages. IAP also attenuated LPS-induced NF-κB binding activity and IκBα phosphorylation/degradation in IECs. Oral administration of IAP significantly reduced the severity of colitis and down-regulated colitis-induced IκBα phosphorylation in IL-10−/− mice.Significance
IAP may inhibit the activation of intestinal epithelial cells and peritoneal macrophages, and may attenuate chronic murine colitis. This finding suggests that IAP supplementation is a potential therapeutic option for inflammatory bowel disease. 相似文献993.
Liquid chromatographic enantiomer separation of several N‐benzyloxycarbonyl (CBZ) and N‐tert‐butoxycarbonyl (BOC) α‐amino acids and their corresponding ethyl esters was performed on covalently immobilized chiral stationary phases (CSPs) (Chiralpak IA and Chiralpak IB) and coated‐type CSPs (Chiralpak AD and Chiralcel OD) based on polysaccharide derivatives. The solvent versatility of the covalently immobilized CSPs in enantiomer separation of N‐CBZ and BOC‐α‐amino acids and their ester derivatives was shown and the chromatographic parameters of their enantioselectivities and resolution factors were greatly influenced by the nature of the mobile phase. In general, standard mobile phases using 2‐propanol and hexane on Chiralpak IA showed fairly good enantioselectivities for resolution of N‐CBZ and BOC‐α‐amino acids and their esters. However, 50% MTBE/hexane (v/v) for resolution of N‐CBZ‐α‐amino acids ethyl esters and 20% THF/hexane (v/v) for resolution of N‐BOC‐α‐amino acids ethyl esters afforded the greatest enantioselectivities on Chiralpak IA. Also, liquid chromatographic comparisons of the enantiomer resolution of these analytes were made on amylose tris(3,5‐dimethylphenylcarbamate)‐derived CSPs (Chiralpak IA and Chiralpak AD) and cellulose tris(3,5‐dimethylphenylcarbamate)‐derived CSPs (Chiralpak IB and Chiralcel OD). Chiralpak AD and/or Chiralcel OD showed the highest enantioselectivities for resolution of N‐CBZ‐α‐amino acids and esters, while Chiralpak AD or Chiralpak IA showed the highest resolution of N‐BOC‐α‐amino acids and esters. Chirality 2009. © 2008 Wiley‐Liss, Inc. 相似文献
994.
Cliques in mitotic spindle network bring kinetochore‐associated complexes to form dependence pathway
Tzu‐Chi Chen Sheng‐An Lee Chen‐Hsiung Chan Yue‐Li Juang Yi‐Ren Hong Yei‐Hsuan Huang Jin‐Mei Lai Cheng‐Yan Kao Chi‐Ying F. Huang 《Proteomics》2009,9(16):4048-4062
The mitotic spindle is an essential molecular machine for chromosome segregation during mitosis. Achieving a better understanding of its organization at the topological level remains a daunting task. To determine the functional connections among 137 mitotic spindle proteins, a protein–protein interaction network among queries was constructed. Many hub proteins, which connect more than one query and serve as highly plausible candidates for expanding the mitotic spindle proteome, are ranked by conventional degree centrality and a new subnetwork specificity score. Evaluation of the ranking results by literature reviews and empirical verification of SEPT6, a novel top‐ranked hub, suggests that the subnetwork specificity score could enrich for putative spindle‐related proteins. Topological analysis of this expanded network shows the presence of 30 3‐cliques and six 4‐cliques (fully connected subgraphs) that, respectively, reside in eight kinetochore‐associated complexes, of which seven are evolution conserved. Notably, these complexes strikingly form dependence pathways for the assembly of the kinetochore complex. These analyses indicate the feasibility of using network topology, i.e. cliques, to uncover novel pathways to accelerate our understanding of potential biological processes. 相似文献
995.
Kuo-Chang Lee Richard I Webb Peter H Janssen Parveen Sangwan Tony Romeo James T Staley John A Fuerst 《BMC microbiology》2009,9(1):5
Background
The phylum Verrucomicrobia is a divergent phylum within domain Bacteria including members of the microbial communities of soil and fresh and marine waters; recently extremely acidophilic members from hot springs have been found to oxidize methane. At least one genus, Prosthecobacter, includes species with genes homologous to those encoding eukaryotic tubulins. A significant superphylum relationship of Verrucomicrobia with members of phylum Planctomycetes possessing a unique compartmentalized cell plan, and members of the phylum Chlamydiae including human pathogens with a complex intracellular life cycle, has been proposed. Based on the postulated superphylum relationship, we hypothesized that members of the two separate phyla Planctomycetes and Verrucomicrobia might share a similar ultrastructure plan differing from classical prokaryote organization. 相似文献996.
Sunggeon Ko Young-Min Lee Weontae Lee 《Biochemical and biophysical research communications》2009,384(2):236-158
Protein tyrosine kinase 6 (PTK6) is composed of SH3, SH2, and Kinase domains, with a linker region (Linker) between the SH2 and Kinase domains. Here, we report the structural basis of the SH3-Linker interaction that results in auto-inhibition of PTK6. The solution structures of the SH3 domain and SH3/Linker complex were determined by NMR spectroscopy. The structure of the SH3 domain forms a conventional β-barrel with two β-sheets comprised of five β-strands. However, the molecular topology and charge distribution of PTK6-SH3 slightly differs from that of the other SH3 domains. The structure of the N-terminal Linker within the complex showed that the proline-rich region (P175-P187) of the Linker forms a compact hairpin structure through hydrophobic interactions. The structure of the SH3/Linker complex revealed intra-molecular interaction between the amino acid pairs R22/E190, W44/W184, N65/P177, and Y66/P179. Mutations in PTK6 at R22, W44, N65, and Y66 residues in the SH3 domain increased catalytic activity compared with wild-type protein, implying that specific interactions between hydrophobic residues in the proline-rich linker region and hydrophobic residues in the SH3 domain are mainly responsible for down-regulating the catalytic activity of PTK6. 相似文献
997.
There is increasing evidence that temperature, in addition to photoperiod, may be an important factor regulating bud dormancy.
The impact of temperature during growth cessation, dormancy development, and subsequent cold acclimation was examined in four
hybrid poplar clones with contrasting acclimation patterns: ‘Okanese’—EARLY, ‘Walker’—INT1, ‘Katepwa’—INT2, and ‘Prairie Sky’—LATE.
Four day–night temperature treatments (13.5/8.5, 18.5/13.5, 23.5/8.5, and 18.5/3.5°C) were applied during a 60-day induction
period to reflect current and predicted future annual variation in autumn temperature for Saskatoon, SK. Warm night temperature
(18.5/13.5°C) strongly accelerated growth cessation, dormancy development, and cold acclimation in all four clones. Day temperature
had the opposite effect of night temperature. Day and night temperatures appeared to act antagonistically against each other
during growth cessation and subsequent dormancy development and cold acclimation. Growth cessation, dormancy development,
and cold acclimation in EARLY and LATE were less affected by induction temperature than INT1 and INT2 suggesting that genotypic
variations exist in response to temperature. Separating specific phenological stages and the impact by temperature on each
clone revealed the complexity of fall phenological changes and their interaction with temperature. Most importantly, future
changes in temperature may affect time to growth cessation, subsequently altering the depth of dormancy and cold hardiness
in hybrid poplar. 相似文献
998.
Sung-Hwan Jo Dal-Hoe Koo Jihyun F Kim Cheol-Goo Hur Sanghyeob Lee Tae-jin Yang Suk-Yoon Kwon Doil Choi 《BMC plant biology》2009,9(1):42
Background
Tandemly repeated DNA, also called as satellite DNA, is a common feature of eukaryotic genomes. Satellite repeats can expand and contract dramatically, which may cause genome size variation among genetically-related species. However, the origin and expansion mechanism are not clear yet and needed to be elucidated. 相似文献999.
Woong-Ki Min Sunggil Kim Soon-Kee Sung Byung-Dong Kim Sanghyeob Lee 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2009,119(7):1289-1299
Cytoplasmic male sterility (CMS), one of the most important traits in crop breeding, is used for commercial F1-hybrid seed production in peppers (Capsicum annuum L.). A nuclear gene, Restorer-of-fertility (Rf), can induce normal pollen production in CMS plants resulting in fertility. Since the first report of fertility restoration
in peppers, various inheritance modes have been suggested, including the presence of a third haplotype of the locus. The pepper
Rf gene has not been cloned, and calculated genetic distances of linked markers have varied between research groups. A more
precise allelic test and additional genetic mapping are needed to accurately select recombinants for use in marker-assisted
backcrossing (MAB). Therefore, the reliability and application of these markers for allelic selection of the Rf gene was tested. Two different F2 populations, Buja and Tamna, were used for the construction of a linkage map. From these linkage groups, a new closely linked
flanking marker of the Rf gene were identified. Previous allelic testing revealed the existence of a third haplotype, Rfls
7701
, which can function as dominant (Rf) or recessive (rf). In a previous report, Rfls
7701
was considered to be linked to unstable male sterility (MS). However, our results suggest that unstable MS was induced by
a gene residing at another locus rather than by Rfls
7701
haplotype-linked allele. 相似文献
1000.