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排序方式: 共有1167条查询结果,搜索用时 15 毫秒
51.
Marco Savioli Lorenzo Antonelli Gianfranco Bocchinfuso Francesca Cavalieri Rita Cimino Emanuela Gatto Ernesto Placidi Julio Raul Fernandez Masso Hilda Garay Perez Hector Santana Maribel Guerra-Vallespi Mariano Venanzi 《Journal of peptide science》2022,28(1):e3356
Synthetic therapeutic peptides (STP) are intensively studied as new-generation drugs, characterized by high purity, biocompatibility, selectivity and stereochemical control. However, most of the studies are focussed on the bioactivity of STP without considering how the formulation actually used for therapy administration could alter the physico-chemical properties of the active principle. The aggregation properties of a 20-mer STP (Ac-His-Ala-Arg-Ile-Lys-D-Pro-Thr-Phe-Arg-Arg-D-Leu-Lys-Trp-Lys-Tyr-Lys-Gly-Lys-Phe-Trp-NH2), showing antitumor activity, were investigated by optical spectroscopy and atomic force microscopy imaging, as itself (CIGB552) and in its therapeutic formulation (CIGB552TF). It has found that the therapeutic formulation deeply affects the aggregation properties of the investigated peptide and the morphology of the aggregates formed on mica by deposition of CIGB552 and CIGB552TF millimolar solutions. Molecular dynamics simulations studied the first steps of CIGB552 aggregation under physiological ionic strength conditions (NaCl 150 mM), showing that peptide oligomers, from dimers to tetramers, are preferentially formed in this environment. Interestingly, cell viability assays performed on H-460 cell lines indicate a major antiproliferative activity of the peptide in its therapeutic formulation with respect to the peptide aqueous solution. 相似文献
52.
Tobias E. Hector Isobel Booksmythe 《Evolution; international journal of organic evolution》2019,73(4):858-859
Research predicting the impact and spread of infectious disease has been heavily influenced by the idea of an evolutionary trade‐off between a pathogen's virulence and its transmission rate. In a meta‐analysis of the key underlying relationships, Acevedo et al. (2019) highlight the surprising lack of empirical evidence for this influential hypothesis. 相似文献
53.
54.
DeLuca HF 《The Journal of steroid biochemistry and molecular biology》2004,(1-5):67-73
Five analogs of 19-nor-1alpha,25-dihydroxyvitamin D(3) are described that show highly selective and potent activities. The 2-methylene-19-nor-(20S)-1alpha25-dihydroxyvitamin D(3) (2MD) and its 2alpha-methyl sister are selectively active on the osteoblast. 2MD is bone anabolic and causes bone formation in vivo and in vitro and is being developed as a therapy for bone loss diseases such as osteoporosis. 2-Methylene-19-nor (20S)-bishomo-1alpha-hydroxypregnacalciferol (2BMP) has no activity on calcium in vivo while totally suppressing circulating parathyroid hormone. Its homologs, i.e. 2-methylene-19-nor-1alpha-hydroxy-homopregnacalciferol (2MP) and 2-methylene-19-nor-1alpha-hydroxypregnacalciferol (2MPC) act similarly but are either less selective (2MP) or not as potent (2MPC). These abbreviated side chain analogs will be developed for diseases where a rise in serum calcium is not desired, as for example, cancer, renal osteodystrophy, psoriasis and autoimmune diseases. 相似文献
55.
56.
Anchoring 9,371 maize expressed sequence tagged unigenes to the bacterial artificial chromosome contig map by two-dimensional overgo hybridization 总被引:17,自引:0,他引:17
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Gardiner J Schroeder S Polacco ML Sanchez-Villeda H Fang Z Morgante M Landewe T Fengler K Useche F Hanafey M Tingey S Chou H Wing R Soderlund C Coe EH 《Plant physiology》2004,134(4):1317-1326
Our goal is to construct a robust physical map for maize (Zea mays) comprehensively integrated with the genetic map. We have used a two-dimensional 24 x 24 overgo pooling strategy to anchor maize expressed sequence tagged (EST) unigenes to 165,888 bacterial artificial chromosomes (BACs) on high-density filters. A set of 70,716 public maize ESTs seeded derivation of 10,723 EST unigene assemblies. From these assemblies, 10,642 overgo sequences of 40 bp were applied as hybridization probes. BAC addresses were obtained for 9,371 overgo probes, representing an 88% success rate. More than 96% of the successful overgo probes identified two or more BACs, while 5% identified more than 50 BACs. The majority of BACs identified (79%) were hybridized with one or two overgos. A small number of BACs hybridized with eight or more overgos, suggesting that these BACs must be gene rich. Approximately 5,670 overgos identified BACs assembled within one contig, indicating that these probes are highly locus specific. A total of 1,795 megabases (Mb; 87%) of the total 2,050 Mb in BAC contigs were associated with one or more overgos, which are serving as sequence-tagged sites for single nucleotide polymorphism development. Overgo density ranged from less than one overgo per megabase to greater than 20 overgos per megabase. The majority of contigs (52%) hit by overgos contained three to nine overgos per megabase. Analysis of approximately 1,022 Mb of genetically anchored BAC contigs indicates that 9,003 of the total 13,900 overgo-contig sites are genetically anchored. Our results indicate overgos are a powerful approach for generating gene-specific hybridization probes that are facilitating the assembly of an integrated genetic and physical map for maize. 相似文献
57.
Sahai A Malladi P Melin-Aldana H Green RM Whitington PF 《American journal of physiology. Gastrointestinal and liver physiology》2004,287(1):G264-G273
The pathogenesis of nonalcoholic steatohepatitis (NASH) is poorly defined. Feeding mice a diet deficient in methionine and choline (MCD diet) induces experimental NASH. Osteopontin (OPN) is a Th1 cytokine that plays an important role in several fibroinflammatory diseases. We examined the role of OPN in the development of experimental NASH. A/J mice were fed MCD or control diet for up to 12 wk, and serum alanine aminotransferase (ALT), liver histology, oxidative stress, and the expressions of OPN, TNF-alpha, and collagen I were assessed at various time points. MCD diet-fed mice developed hepatic steatosis starting after 1 wk and inflammation by 2 wk; serum ALT increased from day 3. Hepatic collagen I mRNA expression increased during 1-4 wk, and fibrosis appeared at 8 wk. OPN protein expression was markedly increased on day 1 of MCD diet and persisted up to 8 wk, whereas OPN mRNA expression was increased at week 4. TNF-alpha expression was increased from day 3 to 2 wk, and evidence of oxidative stress did not appear until 8 wk. Increased expression of OPN was predominantly localized in hepatocytes. Hepatocytes in culture also produced OPN, which was stimulated by transforming growth factor-beta and TNF-alpha. Moreover, MCD diet-induced increases in serum ALT levels, hepatic inflammation, and fibrosis were markedly reduced in OPN(-/-) mice when compared with OPN(+/+) mice. In conclusion, our results demonstrate an upregulation of OPN expression early in the development of steatohepatitis and suggest an important role for OPN in signaling the onset of liver injury and fibrosis in experimental NASH. 相似文献
58.
Recent biodiversity experiments have investigated the relationship between diversity and ecosystem functioning by synthesizing plant communities from pools of species that have been experimentally manipulated to vary numbers and types of species present while holding abiotic factors constant. Biodiversity experiments therefore focus on a previously under-explored aspect of global change: the feedback from diversity to environment. Consequences of random manipulation of species communities may not correspond well to those of specific extinction sequences observed in the past in response to extinction drivers that cause highly non-random loss. However, random manipulation provides a good starting point given that existing communities could undergo many alternative orders of species loss in the future in response to a variety of different potential extinction drivers. Further, the effects of some extinction drivers are currently poorly understood and therefore difficult to predict (e.g. climate change) and it may be premature to dismiss the predictions of random scenarios as irrelevant to all real examples of species loss. The first generations of biodiversity experiments have provided valuable, and sometimes unexpected, discoveries about the general nature of the relationship between diversity and ecosystem functioning. These discoveries could not have been made using observational studies. We propose that different examples of extinction loss in the real or a potential future world form a continuum from situations where the results of the first-generation biodiversity experiments will be highly relevant to less relevant. At the one extreme are examples where the effects of biodiversity on ecosystem functioning will be overwhelmed by direct effects of the extinction driver on processes (e.g. chronic eutrophication). At the other extreme are situations where ecosystem processes are not strongly affected by direct effects of the extinction driver and where the effects of species loss on functioning may be more important (e.g. habitat fragmentation). Given the unprecedented uncertainty about the future of biodiversity and the functioning of ecosystems, a general approach with randomly varying species pools was the right place to start in order to provide a general foundation. The new challenge is to test for effects of biodiversity on functioning in real-world examples of species loss.
Zusammenfassung
Biodiversitätsversuche zeichnen sich dadurch aus, dass natürliche Artenpools experimentell reduziert werden und anschließend der Zusammenhang zwischen der Artenzahl und Ökosystemfunktionen unter konstanten abiotischen Umweltbedingungen untersucht wird. Dadurch unterscheiden sich Biodiversitätsexperimente grundsätzlich von anderen Versuchen, die die Biodiversität als Zielvariable behandeln und stattdessen die abiotische Umwelt manipulieren. Die Auswahl der Arten für die reduzierten Artenpools in Biodiversitätsexperimenten erfolgte bisher meist zufällig, während natürliche Aussterbefaktoren wie Eutrophierung nicht alle Arten gleichermassen gefährden. Für verschiedene Aussterbefaktoren ist aber so wenig bekannt, dass ein zufälliges Aussterbeszenario die beste gegenwärtig verfügbare Option ist. Dies trifft insbesondere für mögliche zukünftige Aussterbeprozesse zu, die durch globale Umweltveränderungen (Klima, biologische Invasionen) oder Habitatsfragmentierung ausgelöst werden könnten. Die erste Generation von Biodiversitätsexperimenten mit zufälligen Aussterbeszenarien hat wertvolle, teilweise unerwartete, generelle Zusammenhänge zwischen Artenzahl und Ökosystemfunktionen aufgedeckt. Diese Zusammenhänge ließen sich durch vergleichende Studien nicht erkennen. In Zukunft sollten Biodiversitätsexperimente dennoch vermehrt Aussterbeszenarien simulieren, die in der realen Umwelt mit größter Wahrscheinlichkeit auftreten. 相似文献59.
Carlos A Aguilar-Salinas Andréia Assis-Luores-Vale Benjamín Stockins Hector Mario Rengifo Dondici José Filho Abrahão Afiune Neto Marcílio Lísia Rabelo Kerginaldo Paulo Torres Egídio Paulo de José Oliveira Carlos Alberto Machado Eliana Reyes Victor Saavedra Fernando Florenzano Ma Victoria Hernández Hernandez Sergio Jiménez Erika Ramírez Cuauhtémoc Vazquez Saul Salinas Ismael Hernández Octavio Medel Ricardo Moreno Paula Lugo Ricardo Alvarado Roopa Mehta Victor Gutierrez Francisco J Gómez Pérez 《Cardiovascular diabetology》2004,3(1):1-6
Background
Microalbuminuria and subsequent progression to proteinuria and nephropathy is associated with increased oxidative stress, increased inflammatory cytokines and increased cardiovascular (CVD) risk. The common functional IL-6 -174G>C gene variant is also associated with elevated levels of inflammatory cytokines and CVD risk.Methods
The aim of this study was to examine the association between the IL-6 -174G>C gene variant with plasma total antioxidant status (TAOS) in 552 subjects with type 2 diabetes in relation to urinary protein excretion.Results
In subjects free from CVD, there was a significant interaction between urinary protein excretion (normoalbuminuria/ microalbuminuria/proteinuria) and the -174C allele (compared to -174GG) in determining plasma TAOS (p value for interaction = 0.03). In the -174C allele carriers there was a significant association between plasma TAOS and urinary protein excretion: normalbuminuria v microalbuminuria v proteinuria: 44.30% ± 11.32 vs. 39.74% ± 14.83 vs. 37.93% ± 16.42, ANOVA p = 0.025. In those with CVD, no interaction or association was observed with the -174C allele (p = 0.246).Conclusion
The IL-6 -174G>C gene variant is associated with differences in plasma oxidative stress in response to altered protein excretion in subjects with type 2 diabetes. 相似文献60.
Plank DM Yatani A Ritsu H Witt S Glascock B Lalli MJ Periasamy M Fiset C Benkusky N Valdivia HH Sussman MA 《American journal of physiology. Heart and circulatory physiology》2003,285(1):H305-H315
Changes in calcium (Ca2+) regulation contribute to loss of contractile function in dilated cardiomyopathy. Clinical treatment using beta-adrenergic receptor antagonists (beta-blockers) slows deterioration of cardiac function in end-stage heart failure patients; however, the effects of beta-blocker treatment on Ca2+ dynamics in the failing heart are unknown. To address this issue, tropomodulin-overexpressing transgenic (TOT) mice, which suffer from dilated cardiomyopathy, were treated with a nonselective beta-receptor blocker (5 mg. kg-1. day-1 propranolol) for 2 wk. Ca2+ dynamics in isolated cardiomyocytes of TOT mice significantly improved after treatment compared with untreated TOT mice. Frequency-dependent diastolic and Ca2+ transient amplitudes were returned to normal in propranolol-treated TOT mice and but not in untreated TOT mice. Ca2+ kinetic measurements of time to peak and time decay of the caffeine-induced Ca2+ transient to 50% relaxation were also normalized. Immunoblot analysis of untreated TOT heart samples showed a 3.6-fold reduction of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), whereas Na+/Ca2+ exchanger (NCX) concentrations were increased 2.6-fold relative to nontransgenic samples. Propranolol treatment of TOT mice reversed the alterations in SERCA and NCX protein levels but not potassium channels. Although restoration of Ca2+ dynamics occurred within 2 wk of beta-blockade treatment, evidence of functional improvement in cardiac contractility assessed by echocardiography took 10 wk to materialize. These results demonstrate that beta-adrenergic blockade restores Ca2+ dynamics and normalizes expression of Ca2+-handling proteins, eventually leading to improved hemodynamic function in cardiomyopathic hearts. 相似文献