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151.
Yong-Jin Wu Jason Guernon Andrea McClure Brian Venables Ramkumar Rajamani Kevin J. Robbins Ronald J. Knox Michele Matchett Rick L. Pieschl James Herrington Linda J. Bristow Nicholas A. Meanwell Richard Olson Lorin A. Thompson Carolyn Dzierba 《Bioorganic & medicinal chemistry letters》2018,28(5):958-962
Replacement of the piperidine ring in the lead benzenesulfonamide Nav1.7 inhibitor 1 with a weakly basic morpholine core resulted in a significant reduction in Nav1.7 inhibitory activity, but the activity was restored by shortening the linkage from methyleneoxy to oxygen. These efforts led to a series of morpholine-based aryl sulfonamides as isoform-selective Nav1.7 inhibitors. This report describes the synthesis and SAR of these analogs. 相似文献
152.
D. A. Gust T. P. Gordon W. F. Gergits N. J. Casna K. G. Gould H. M. McClure 《Primates; journal of primatology》1996,37(3):271-278
Paternity of 16 pigtail macaque offspring was determined using a DNA profile analysis and was based on two independent assays
of the genome of each individual using multilocus DNA probes. The offspring were members of a group of 59 pigtail macaques,
including 5 adult males, 1 subadult male, and 37 adult and subadult females. Rank was unrelated to paternity as the first
ranking male sired 0, the second ranking male sired 3; the third ranking male sired 0, the fourth ranking male sired 8, and
the fifth ranking male sired 2 offspring. The subadult male sired 0 offspring. The DNA analysis was effective in excluding
possible sires of 3 offspring whose mothers had become pregnant by another male before being introduced to the study males.
Subsequent semen evaluation revealed an absence of sperm in the semen of the alpha male, but revealed a sperm count within
normal limits in the third ranking male, who also sired no offspring. Behavioral data focusing on male-offspring interactions
found that offspring did not preferentially affiliate with their sire and that males did not affiliate with their offspring
frequently enough for analysis. Thus, this study of one captive pigtail macaque group demonstrates that: (1) rank was not
a predictor of reproductive success; and (2) there was no preferential attraction for one's own offspring by males or one's
own sire by offspring. 相似文献
153.
In common with oncoviruses but unlike the lentivirus human immunodeficiency virus type 1, foamy (spuma) viruses require host cell proliferation for productive infection. We show that human immunodeficiency virus type 1 replicates in RD-CD4 cells regardless of the growth arrest condition of the cells, while murine leukemia virus is unable to infect growth-arrested RD-CD4 cells or cells progressing through a partial cell cycle that includes S phase but not mitosis. Human foamy virus, like murine leukemia virus, does not productively infect G1/S or G2 growth-arrested cells. Two other foamy viruses, simian foamy virus type 1, isolated from a macaque, and simian foamy virus type 6, isolated from a chimpanzee, also fail to establish productive infection in G1/S-arrested cells. 相似文献
154.
Thomas Folks Thomas Rowe Francois Villinger Bharat Parekh Ann Mayne Daniel Anderson Harold McClure Aftab A. Ansari 《Journal of medical primatology》1997,26(4):181-189
Abstract: A number of rhesus macaques experimentally infected with SIV isolates such as SIVmac251, fail to seroconvert, develop high plasma viremia and die rapidly (within 6–7 months p.i.). We hypothesized that such rapid progression is a result of a state of hyperimmune activation and concomitant immune suppression of these animals at the time of virus challenge. In efforts to test the hypothesis that immune activation leads to rapid progression of lentivirus-induced disease, adult rhesus macaques were infected with SIVmac251 and received an alternate monthly schedule of repeated immunization with allogeneic cells, keyhole limpet hemocyanin and tetanus toxoid (group I). For purposes of controls, a group of monkeys was infected with the same pool and dose of virus but were not immunized (group II) and a group was immunized with the same schedule of multiple antigens as group I but were not infected with SIV (group III). All the animals in group I (n ? 3) either failed to seroconvert or developed very low levels of SIV antibodies, had high plasma p27 defined antigenemia, and died within 8 months (2/3 died within 4 months). Of the animals in group II (n = 8), two patterns emerged as we had noted before. One subgroup (3 animals), displayed the same profile as group I (failure to fully seroconvert, high p27 levels and death by 8 months), whereas the other subgroup (5 animals) seroconverted, had low plasma p27 levels, and survived past 11 months (2/5 still alive past 22 months). All 3 animals in group III remained healthy. The data provided herein suggest that either experimental or natural (due to factors not clear at present) immune stimulation may lead to accelerated lentivirus induced disease progression most likely due to immune suppression and has implications for the understanding of the mechanisms for the rate of disease progression in human HIV-1 infection. 相似文献
155.
Cultured chondrocytes derived from the caudal and cephalic ends of embryonic chick sterna have been compared with each other
and with whole sternum, by using a panel of 21 lectins to probe the distribution of oligosaccharides in glycoconjugates of
cells and matrix at various times of culture or development. On culture in collagen gels, the cells changed their morphology
with time, degrading glycan in the surrounding culture medium and depositing new matrix, the glycan content of which reflected
the site of origin of the cells, indicating that the glycan phenotype of both cells and matrix (‘glycotype’) was predetermined
and persistent. Sterna of embryonic chicks showed unexpected complexity in their distribution pattern of glycan, containing
at least six distinct regions. Major regional temporal differences were evident among saccharides terminating in α-N-acetyl
galactosamine and β-galactose, while changes in glycans terminating in fucose, sialic acid and α-mannose were somewhat less
marked. Subsets of complex N-glycans changed little.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
156.
Katerina Dvorakova Robert T. Dorr Alfred Gallegos Thomas McClure Garth Powis 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,696(2):1304
Oryzalin [3,5-dinitro-N,N-di(n-propyl)benzensulfanilamide] is a widely used sulfonamide herbicide that selectively inhibits microtubule formation in algae and higher plants. Oryzalin has also been found to be an inhibitor of intracellular free Ca2+ signalling in mammalian cells and to have antitumor activity in animals. Despite its widespread use there have been no reports of the pharmacokinetics of oryzalin in animals or man. A reversed-phase high-performance liquid chromatographic (HPLC) method was developed to measure oryzalin in biological fluids. Following repeated daily administration of oryzalin to mice by the i.p. route to 200 mg/kg, or the p.o. route at 300 mg/kg, peak plasma concentrations of up to 25 μg/ml were achieved. The half life for oryzalin in plasma of mice given i.p. oryzalin was 14.3 h with a clearance of 0.07 1/h. A major metabolite of oryzalin, N-depropyloryzalin, was identified in plasma and its structure confirmed by mass spectral analysis (M+H+ = 305). This metabolite was cleared more rapidly than oryzalin with a half life of 1.15 h and a clearance of 0.17 1/h. N-Depropylorryzalin caused similar inhibition of colony formation by HT-29 colon cancer cells as oryzalin with IC50 = 8 μg/ml. The results suggest that oryzalin and its N-depropyl metabolite can inhibit tumor colony formation at pharmacologically achievable levels. 相似文献
157.
Mutations in two pollen self‐incompatibility factors in geographically marginal populations of Solanum habrochaites impact mating system transitions and reproductive isolation
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158.
Rapid biomonitoring protocols, using biotic indices based on macroinvertebrate diversity to assess river ecosystem health, are widely used globally. Such quick assessment techniques are lauded for the rapid results obtained and the relatively easy protocol used to achieve an answer. However, do such quick assessments of water quality give enough information about ecosystems? Are important details being overlooked? When should a full faunal survey be used in preference? Important research programmes, including environmental impact studies, often misuse biomonitoring techniques, making influential management decisions using superficial, low-level data obtained using biomonitoring tools, inappropriate to address those management objectives. The value of using biomonitoring as a quick tool, versus a more detailed faunal assessment, is considered here. The assessment of teloganodid mayfly fauna occurring in South African rivers provides an example of the value of detailed studies versus superficial family level investigations, showing that a rapid biomonitoring approach should not be used as a shortcut when a more detailed survey is needed. Each situation should be assessed for its own merit in a given set of project circumstances. A checklist of criteria is presented, giving guidance on when rapid biomonitoring alone is valuable and when more detailed assessments would give a more relevant result. 相似文献
159.
160.
An intercellular washing solution containing about 1% of the soluble protein, 0.3% or less of the glucose-6-phosphate dehydrogenase activity, but up to 20% of the peroxidase and β-d-glucosidase activity of barley (Hordeum vulgare L.) or oat (Avena sativa L.) primary leaves was obtained by vacuum infiltrating peeled leaves with pH 6.9 buffered 200 millimolar NaCl. After this wash, segments were homogenized in buffer, centrifuged, and the supernatant was assayed for soluble cytoplasmic enzymes. The pellet was washed and resuspended in 1 molar NaCl to solubilize enzymes strongly ionically bound to the cell wall. The final pellet was assayed for enzyme activity covalently bound in the cell wall. Apoplastic (intercellular washing solution, ionically bound, and covalently bound) fractions contained up to 76% of the β-d-glucosidase activity, 36% of the peroxidase activity, 11% of the nonspecific arylesterase activity, 4% of the malate dehydrogenase activity, but less than 2% of the glucose-6-phosphate dehydrogenase activity of peeled leaf segments. The partitioning and salt-solubility of the enzymes between the apoplast and symplast differed considerably between these two species. Intercellular washing fluid prepared by centrifuging unpeeled leaves had higher activity for glucose-6-phosphate dehydrogenase, less soluble protein, and less peroxidase activity per leaf than intercellular washing solution obtained by our peeling-infiltration-washing technique. The results are discussed in relation to the roles of these enzymes in phenolic metabolism in the cell wall. 相似文献