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991.
A selection of 76 nitroheterocycles and related compounds from our in-house compound library was screened in vitro against the parasite Trypanosoma brucei rhodesiense, causative agent of human African trypanosomiasis (HAT). The unspecific cytotoxicity of the compounds was also evaluated against rat myoblast L6-cells to measure the selectivity of the compounds towards the parasite. This screening revealed some preliminary structure-activity relationships (SAR) among the series, and six hit compounds showing interesting activity (IC(50)≤10μM) and fair selectivity (SI>17). The 7-nitroquinoxalin-2-one and 5-nitroindazole scaffold derivatives 58 and 35, respectively, are particularly interesting because of their established oral bioavailability in mice. These hits represent interesting starting points for a medicinal project aimed at identifying the SAR behind this class of compounds. 相似文献
992.
Molecular Ecology Resources Primer Development Consortium Abreu AG Albaina A Alpermann TJ Apkenas VE Bankhead-Dronnet S Bergek S Berumen ML Cho CH Clobert J Coulon A DE Feraudy D Estonba A Hankeln T Hochkirch A Hsu TW Huang TJ Irigoien X Iriondo M Kay KM Kinitz T Kothera L LE Hénanff M Lieutier F Lourdais O Macrini CM Manzano C Martin C Morris VR Nanninga G Pardo MA Plieske J Pointeau S Prestegaard T Quack M Richard M Savage HM Schwarcz KD Shade J Simms EL Solferini VN Stevens VM Veith M Wen MJ 《Molecular ecology resources》2012,12(2):374-376
This article documents the addition of 139 microsatellite marker loci and 90 pairs of single‐nucleotide polymorphism sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Aglaoctenus lagotis, Costus pulverulentus, Costus scaber, Culex pipiens, Dascyllus marginatus, Lupinus nanus Benth, Phloeomyzus passerini, Podarcis muralis, Rhododendron rubropilosum Hayata var. taiwanalpinum and Zoarces viviparus. These loci were cross‐tested on the following species: Culex quinquefasciatus, Rhododendron pseudochrysanthum Hay. ssp. morii (Hay.) Yamazaki and R. pseudochrysanthum Hayata. This article also documents the addition of 48 sequencing primer pairs and 90 allele‐specific primers for Engraulis encrasicolus. 相似文献
993.
Thomas J. Schmidt Sebastian Rzeppa Marcel Kaiser Reto Brun 《Phytochemistry letters》2012,5(3):632-638
The dichloromethane extract of Larrea tridentata (Creosote bush, Zygophyllaceae) showed activity against the protozoan pathogens Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum (IC50 2.8, 14.6, 5.2, 2.9 μg/ml, cytotoxicity against L6 rat skeletal myoblasts: 25.4 μg/ml).In search for potentially active constituents, nine lignans (three dibenzylbutanes, four epoxylignans, two aryltetralins), six flavonoids and one ester of ferulic acid (3′-oxohexylferulate) were isolated and identified by spectroscopic methods.Since some ambiguities with respect to the absolute configuration of several chiral lignans from L. tridentata were found in the literature, CD spectra were recorded and correlated with results from quantum mechanical spectra simulations (TD-DFT at the B3LYP/6-31D(d,p) level). Thereby, the absolute stereochemistry of these lignans can now be assigned with certainty.The activity of the isolated constituents against the protozoan parasites was investigated. The major lignan meso-nordihydroguaiaretic acid (NDGA), mainly responsible for the anti-inflammatory effects of this plant, was found to be the most active compound (IC50 values: 4.5, 33.1, 12.0 and 7.7 μM against the mentioned parasites, respectively, 33.1 μM for cytotoxicity against L6 rat skeletal myoblasts). Although its level of activity is only moderate, NDGA can thus also be considered the main active compound for the antiprotozoal activity of L. tridentata. 相似文献
994.
995.
Blažek J Jansa P Baszczyňski O Kaiser MM Otmar M Krečmerová M Drančínský M Holý A Králová B 《Bioorganic & medicinal chemistry》2012,20(9):3111-3118
A new enzymatic method for the synthesis of β-galactosides of nucleosides and acyclic nucleoside analogues has been developed, using β-galactosidase from Escherichia coli as a catalyst and lactose as a sugar donor. The method is very rapid, feasible and last but not least inexpensive. Its applicability has been proven for a broad variety of possible substrates with respect to its scaling up for preparative use. Five new compounds from a series of nucleoside and acyclic nucleoside analogues have been prepared on a scale of several hundred milligrams, in all cases revealing very good results of the method concerning the reproducibility of the reaction yields and simplicity of the purification process. 相似文献
996.
This study was designed to evaluate in suckling early pregnant beef cows with and without eCG-pre-stimulation: (i) the influence of day gestation (from 40 to 101 days) and the consecutive eCG treatments on the follicular growth induced by means of ultrasound-guided transvaginal follicle ablation (FA; all follicles ≥ 5 mm) and the number and quality oocytes recovered by ovum pick-up (OPU) and (ii) the possible effects of repeated hormonal stimulation and FA/OPU on pregnancy outcome. Twelve suckling early pregnant Angus cows (40 days post fixed-time artificial insemination) were randomly assigned to each of two groups (n=6 group(-1)). Group 1 treatments included: FA (Day 0), eCG (1600 IU; Day 1) and OPU (Day 5). Group 2: as cited Group 1 with no eCG treatment. In both groups, OPU was repeated five times (Days 45, 59, 73, 87 and 101 of gestation). The numbers (mean ± SEM) of class II (5-9 mm; 4.3 ± 0.9) and class III (≥10 mm; 2.5 ± 0.4) follicles visualized per cow per OPU session in eCG-treated cows were greater (P<0.05) than for non-treated cows (0.9 ± 0.1 and 0.9 ± 0.1, respectively). In contrast, the number (mean ± SEM) of class I (<5mm) follicles per cow per OPU session was lower for cows with eCG treatment (2.8 ± 0.4) than for non-treated cows (5.7 ± 0.5). The mean number of aspirated follicles was not significantly different (P<0.05) between eCG-treated cows and non-treated cows at 45 and 59 days of pregnancy. However, the mean number of aspirated follicles was greater (P=0.03) in eCG-treated cows than non-treated cows from 73 day of pregnancy onwards. The numbers (mean ± SEM) of recovered oocytes and viable oocytes/cow/session were greater (P<0.05) for eCG-treated cows (2.2 ± 0.2 and 1.6 ± 0.4, respectively) than for non-treated cows (1.0 ± 0.2 and 0.9 ± 0.2, respectively). No donor pregnancies were lost either during or following OPU procedure. We can conclude that (1) eCG-treated pregnant suckled cows can be a source of oocytes for IVF at least to 100 days of gestation and (2) repeated FA/eCG treatment/OPU procedures did not affect the pregnancy outcome. 相似文献
997.
Clinical and reproductive consequences of using BVDV-contaminated semen in artificial insemination in a beef herd in Argentina 总被引:1,自引:0,他引:1
EA González Altamiranda GG Kaiser N Weber MR Leunda A Pecora DA Malacari O Morán CM Campero AC Odeón 《Animal reproduction science》2012,133(3-4):146-152
The current report was prompted by an atypical outbreak of mucosal disease that occurred in a beef herd in the southwestern part of Buenos Aires Province, Argentina, where a total of 9/41 (21.9%) yearling bulls died. Blood samples from 73 bulls and 189 heifers were tested for evidence of persistent BVDV infection with Bovine Viral Diarrhea Virus (BVDV). Non-cytopathic BVDV was isolated from 7 (9.6%) 24- to 36-month-old bulls, and 3 (1.6%) 36-month-old heifers. Non-cytopathic BVDV was also detected in the seminal plasma of three of six persistently infected (PI) bulls. Furthermore, a 171bp genomic fragment of BVDV was consistently detected by nested RT-PCR in one of the two samples of the commercial semen used for artificial insemination, indicating that this semen could be a possible source of infection for the whole herd. To evaluate the possible reproductive consequences of PI heifers and bulls, ovaries and semen were obtained from PI cattle for in vitro assays. The in vitro fertilization of oocytes with semen from PI bulls was associated with decreased cleavage and embryo development rates. Additionally, non-cytopathic BVDV was isolated from the follicular fluid of PI heifers. Genetic typing revealed that all isolates BVDV from the present study had a high percentage of homology and that all of the fragments from the RT-PCR clearly fit with the BVDV 1b cluster. These findings confirm the negative impact that BVDV can have on the reproductive performance of cattle and the importance of applying the proper sanitary controls to minimize the risk of BVDV infection. 相似文献
998.
Barth BM Gustafson SJ Hankins JL Kaiser JM Haakenson JK Kester M Kuhn TB 《Cellular signalling》2012,24(6):1126-1133
A persistent inflammatory reaction is a hallmark of chronic and acute pathologies in the central nervous system (CNS) and greatly exacerbates neuronal degeneration. The proinflammatory cytokine tumor necrosis factor alpha (TNFα) plays a pivotal role in the initiation and progression of inflammatory processes provoking oxidative stress, eicosanoid biosynthesis, and the production of bioactive lipids. We established in neuronal cells that TNFα exposure dramatically increased Mg(2+)-dependent neutral sphingomyelinase (nSMase) activity thus generating the bioactive lipid mediator ceramide essential for subsequent NADPH oxidase (NOX) activation and oxidative stress. Since many of the pleiotropic effects of ceramide are attributable to its metabolites, we examined whether ceramide kinase (CerK), converting ceramide to ceramide-1-phosphate, is implicated both in NOX activation and enhanced eicosanoid production in neuronal cells. In the present study, we demonstrated that TNFα exposure of human SH-SY5Y neuroblastoma caused a profound increase in CerK activity. Depleting CerK activity using either siRNA or pharmacology completely negated NOX activation and eicosanoid biosynthesis yet, more importantly, rescued neuronal viability in the presence of TNFα. These findings provided evidence for a critical function of ceramide-1-phospate and thus CerK activity in directly linking sphingolipid metabolism to oxidative stress. This vital role of CerK in CNS inflammation could provide a novel therapeutic approach to intervene with the adverse consequences of a progressive CNS inflammation. 相似文献
999.
1000.