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81.
《Bioorganic & medicinal chemistry》2016,24(10):2242-2250
Suppression of glucose reabsorption through the inhibition of sodium-dependent glucose co-transporter 2 (SGLT2) is a promising therapeutic approach for the treatment of type 2 diabetes. To investigate the effect of C6-substitution on inhibition of SGLT2 by N-indolylglucosides, a small library of 6-triazole, 6-amide, 6-urea, and 6-thiourea N-indolylglycosides were synthesized and tested. A detailed structure–activity relationship (SAR) study culminated in the identification of 6-amide derivatives 6a and 6o as potent SGLT2 inhibitors, which were further tested for inhibitory activity against SGLT1. The data obtained indicated that 6a and 6o are mildly to moderately selective for SGLT2 over SGLT1. Both compounds were also evaluated in a urinary glucose excretion test and pharmacokinetic study; 6a was found capable of inducing urinary glucose excretion in normal SD rats. 相似文献
82.
Autotaxin (ATX) is an attractive target for the anticancer therapeutics that inhibits angiogenesis, invasion and migration. ATX is an extracellular lysophospholipase D that hydrolyzes lysophosphatidylcholine to form the bioactive lipid lysophosphatidic acid. The aromatic phosphonate S32826 was the first described nanomolar inhibitor of ATX. However, the tridecylamide substituent on aromatic ring contributed to its poor solubility and bioavailability, severely limiting its utility in vivo. c Log P calculations revealed that the lipophilicity of S32826 could be lowered by shortening its hydrophobic chain and by introducing substituents alpha to the phosphonate. Herein, we describe the synthesis of a small set of α-substituted phosphonate analogs of S32826, and we show that shortening the chain and adding α-halo or α-hydroxy substituents increased solubility; however, ATX inhibition was reduced by most substitutions. An optimal compound was identified for examination of biological effects of ATX inhibition in vivo. 相似文献
83.
84.
Patterns of species richness on very small islands: the plants of the Aegean archipelago 总被引:4,自引:0,他引:4
Maria Panitsa Dimitrios Tzanoudakis Kostas A. Triantis Spyros Sfenthourakis 《Journal of Biogeography》2006,33(7):1223-1234
Aim To investigate the species–area relationship (SAR) of plants on very small islands, to examine the effect of other factors on species richness, and to check for a possible Small Island Effect (SIE). Location The study used data on the floral composition of 86 very small islands (all < 0.050 km2) of the Aegean archipelago (Greece). Methods We used standard techniques for linear and nonlinear regression in order to check several models of the SAR, and stepwise multiple regression to check for the effects of factors other than area on species richness (‘habitat diversity’, elevation, and distance from nearest large island), as well as the performance of the Choros model. We also checked for the SAR of certain taxonomic and ecological plant groups that are of special importance in eastern Mediterranean islands, such as halophytes, therophytes, Leguminosae and Gramineae. We used one‐way anova to check for differences in richness between grazed and non‐grazed islands, and we explored possible effects of nesting seabirds on the islands’ flora. Results Area explained a small percentage of total species richness variance in all cases. The linearized power model of the SAR provided the best fit for the total species list and several subgroups of species, while the semi‐log model provided better fits for grazed islands, grasses and therophytes. None of the nonlinear models explained more variance. The slope of the SAR was very high, mainly due to the contribution of non‐grazed islands. No significant SIE could be detected. The Choros model explained more variance than all SARs, although a large amount of variance of species richness still remained unexplained. Elevation was found to be the only important factor, other than area, to influence species richness. Habitat diversity did not seem important, although there were serious methodological problems in properly defining it, especially for plants. Grazing was an important factor influencing the flora of small islands. Grazed islands were richer than non‐grazed, but the response of their species richness to area was particularly low, indicating decreased floral heterogeneity among islands. We did not detect any important effects of the presence of nesting seabird colonies. Main conclusions Species richness on small islands may behave idiosyncratically, but this does not always lead to a typical SIE. Plants of Aegean islets conform to the classical Arrhenius model of the SAR, a result mainly due to the contribution of non‐grazed islands. At the same time, the factors examined explain a small portion of total variance in species richness, indicating the possible contribution of other, non‐standard factors, or even of stochastic effects. The proper definition of habitat diversity as pertaining to the taxon examined in each case is a recurrent problem in such studies. Nevertheless, the combined effect of area and a proxy for environmental heterogeneity is once again superior to area alone in explaining species richness. 相似文献
85.
Parental contribution and coefficient of coancestry among maize inbreds: pedigree, RFLP, and SSR data 总被引:3,自引:0,他引:3
R. Bernardo J. Romero-Severson J. Ziegle J. Hauser L. Joe G. Hookstra R. W. Doerge 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2000,100(3-4):552-556
The genetic relationship between inbreds i and j can be estimated from pedigree or from molecular marker data. The objectives of this study were to: (1) determine whether
pedigree, restriction fragment length polymorphism (RFLP), and simple sequence repeat (SSR) data give similar estimates of
parental contribution and coefficient of coancestry (f
ij
) among a set of maize (Zea mays L.) inbreds, and (2) compare the usefulness of RFLP and SSR markers for estimating genetic relationship. We studied 13 maize
inbreds with known pedigrees. The inbreds were genotyped using 124 RFLP and 195 SSR markers. For each type of marker, parental
contributions were estimated from marker similarity among an inbred and both of its parents, and were subsequently used to
estimate f
ij
. Estimates of parental contribution differed significantly (α<0.05) between pedigree data and either type of marker, but
not between the marker systems. The RFLP estimates of parental contribution failed to sum to 1.0, reflecting a higher frequency
of non-parental bands with RFLP than with SSR markers. The f
ij
estimated from pedigree, RFLP, and SSR data were highly correlated (r=0.87–0.97), although significant differences were found among the three sets of f
ij
estimates. We concluded that pedigree and marker data often lead to different estimates of parental contribution and f
ij
, and that SSR markers are superior to RFLP markers for estimating genetic relationship. A relevant question is whether or
not the inbreds previously genotyped with an older marker system (e.g., RFLP) need to be re-analyzed with a newer marker system
(e.g., SSR) for the purpose of estimating genetic relationship. Such re-analysis seems unnecessary if data for the same type
of marker are available for a given inbred and both of its parents.
Received: 2 June 1999 / Accepted: 30 July 1999 相似文献
86.
石杉碱甲结构改造的研究进展 总被引:1,自引:0,他引:1
石杉碱甲是高效、高选择性的可逆性乙酰胆碱酯酶抑制剂,是治疗早老性痴呆症的一个有前景的药物.本文概述了石杉碱甲的性质、结构和构效关系,从结构简化、C10、吡啶酮环、脂桥环、环外双键和桥头氨基等方面综述了石杉碱甲结构改造的研究进展,并描述了所得的新型石杉碱甲类似物的抗乙酰胆碱酯酶的生物活性.在已合成的大量的石杉碱甲类似物中,部分类似物的活性优于天然石杉碱甲,石杉碱甲结构改造的研究取得了可喜的进展. 相似文献
87.
鞭毛介导的运动性与细菌生物膜的相互关系 总被引:3,自引:0,他引:3
摘要:由于运动缺陷型细菌形成生物膜的能力会下降,长期以来细菌的运动性都被认为与生物膜的形成呈正相关,但这一理论现在证明还有待商榷,而且运动性不是影响膜形成的绝对因素。本文详细介绍了细菌的生物膜和运动性,并重新定义了两者的相互关系。 相似文献
88.
Ethan P. White 《Ecology letters》2004,7(4):329-336
The species–time relationship (STR) is a macroecological pattern describing the increase in the observed species richness with the length of time censused. Understanding STRs is important for understanding the ecological processes underlying temporal turnover and species richness. However, accurate characterization of the STR has been hampered by the influence of sampling. I analysed STRs for 521 breeding bird survey communities. I used a model of sampling effects to demonstrate that the increase in richness was not due exclusively to sampling. I estimated the time scale at which ecological processes became dominant over sampling effects using a two‐phase model combining a sampling phase and either a power function or logarithmic ecological phase. These two‐phase models performed significantly better than sampling alone and better than simple power and logarithmic functions. Most community dynamics were dominated by ecological processes over scales <5 years. This technique provides an example of a rigorous, quantitative approach to separating sampling from ecological processes. 相似文献
89.
The hemocytes of Rhodnius prolixus were analyzed during the course of infection with the protozoan Trypanosoma rangeli. The following cell types were identified: prohemocyte, plasmatocyte, adipocyte, granular cell and oenocytoid. The number of these cells changes during the infection course thus indicating a cell response to infection of R. prolixus by T. rangeli. Transmission electron microscopy showed that plasmatocytes were able to ingest epimastigote forms of the parasite, which were then found within a parasitophorous vacuole. Amorphous material was seen within the vacuole suggesting that fusion of host cell lysosomes with the vacuole took place. Intravacuolar parasites in process of digestion were observed. In addition, reaction product indicative of the presence of acid phosphatase was observed in parasite-containing vacuoles. No dividing parasites were seen within the vacuole in contrast to what was observed outside the host cells. 相似文献
90.
Ethanol Inhibits Basic Fibroblast Growth Factor-Mediated Proliferation of C6 Astrocytoma Cells 总被引:2,自引:0,他引:2
Abstract: Early ethanol exposure alters the proliferative activity of glial and neuronal precursors in the developing CNS. The present study tests the hypothesis that ethanol-induced alterations in cell proliferation result from interference with growth factors. An in vitro model of astroglia (C6 astrocytoma cells) was used to study the effects of ethanol on proliferation mediated by basic fibroblast growth factor (bFGF). bFGF stimulated the proliferation of C6 cells. This bFGF-enhanced proliferation was evident by increases in total cell number, DNA synthesis (as measured by [3 H]thymidine incorporation), and the number of cells that took up bromodeoxyuridine. A synthetic peptide that specifically blocked the binding of bFGF to its high-affinity receptor completely abolished the proliferation-promoting effect of bFGF. The action of another mitogen for C6 cells, insulin-like growth factor-1, was not affected by this peptide. Therefore, the bFGF-stimulated proliferation was mediated through a specific bFGF receptor. Ethanol inhibited bFGF-mediated proliferation in a concentration-dependent manner. Ethanol concentrations of 100 and 200 mg/dl partially inhibited bFGF-mediated proliferation (by 58 and 74%, respectively), whereas concentrations of ≥400 mg/dl completely abolished the growth-stimulating effect of bFGF. Our data show that ethanol alters proliferative activity of C6 cells by disrupting the action of bFGF. The target of ethanol neurotoxicity is a receptor-mediated activity. bFGF can affect cell proliferation by a non-receptor-mediated intracellular pathway, but ethanol does not have an impact on this pathway. 相似文献