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961.
《Expert review of proteomics》2013,10(5):561-572
Cystine-knot miniproteins, also known as knottins, constitute a large family of structurally related peptides with diverse amino acid sequences and biological functions. Knottins have emerged as attractive candidates for drug development as they potentially fill a niche between small molecules and protein biologics, offering drug-like properties and the ability to bind to clinical targets with high affinity and selectivity. Due to their extremely high stability and unique structural features, knottins also demonstrate promise in addressing challenging drug development goals, including the potential for oral delivery and the ability to access intracellular drug targets. Several naturally-occurring knottins have recently received approval for treating chronic pain and irritable bowel syndrome, while others are under development for tumor imaging applications. To expand beyond nature’s repertoire, rational and combinatorial protein engineering methods are generating tumor-targeting knottins for use as cancer diagnostics and therapeutics. 相似文献
962.
Different genetic stains of avian RNA tumor virus (ATV) were labeled with the fluorescent membrane probe R-18 (rhodamine conjugated
to a hydrocarbon chain) and cellular receptors for virus infection were analyzed on a rapid, single-cell basis by a multiparameter
cell sorter. Chicken cells genetically susceptible to various R-18 ATV were found to adsorb much more virus, as measured by
increased fluorescent binding, than did genetically resistant chicken cells. Virus binding to receptor sites could be saturated
with increased concentrations of labeled virus. This binding could be altered by removal of the polycation, polybrene, indicating
the important influence of electrostatic forces. Correlated time measurements of virus binding to single cells were taken
with these fluorescence measurements allowing for a minute-to-minute study of the kinetics of viral adsorption to resistant
and susceptible cells. The ratio of fluorescence (proportional to the number of virions bound per cell) to light scatter (proportional
to cell surface area) on a cell-to-cell basis was analyzed to examine the heterogeneity in fluorescent virion bound per unit
cell surface area within a given cell type. With these calculations, it was found that a large amount, but not all, of observed
fluorescence heterogeneity merely reflects differences in cell surface areas. However, there are significant differences in
viral receptor site densities within this supposedly homogeneous population of cells. This study represents a successful application
of fluorescent membrane probes and flow cytometry to the study of cellular responses to viral infection at the single-cell
level. Sine large numbers of cells can be examined rapidly, small subpopulations of live virally susceptible or resistant
cells can be cloned by multiparameter cell sorting. 相似文献
963.
Leonard A. Cohen 《In vitro cellular & developmental biology. Plant》1982,18(6):565-575
Summary A new in vitro model for human breast cancer is described. Derived from anN-nitrosomethylurea (NMU) induced rat mammary adenocarcinoma, this serially cultivated cell line has been demonstrated, by
a variety of criteria, to be an authentic neoplastic, rat mammary epithelial cell line. The criteria used include morphological
and growth characteristics; the presence of specific cell surface antigens; steroid hormone receptors; hormone responsiveness;
casein production; karyotype and isoenzyme profile analysis; anchorage independent growth and oncogenicity. Inasmuch as the
NMU cell line possesses high concentrations of glucocorticoid and androgen receptors, it may provide a useful model for study
of the action of these hormones in human breast cancer. In addition, the NMU line may serve as a valuable in vitro model in
which to assess the effects of a variety of endogenous and exogenous agents known to influence mammary tumor growth in vivo,
including drugs, nutrients, and growth factors.
This work was supported by Grants CA29602 and RR05775-05 from the National Cancer Institute, Bethesda, Maryland. 相似文献
964.
Effects of larval age and prolonged simulated acid rain on the susceptibility of European pine sawfly to virus infection 总被引:2,自引:0,他引:2
We studied the effect of simulated acid rain treatment of host trees on the susceptibility of the European pine sawfly larvae to virus, and possible differences when larvae of two different ages were infected. Older larvae were less susceptible to virus. Most larvae treated with virus 2 days after they started feeding on experimental foliage (group A) died rapidly within 10 days after the virus treatment, and survival to the end of the larval period was only 8–25%. Larvae treated with virus 1 week later (group B) were less affected by the virus and 36–49% survived. In group A the larval survival in the pH 3 treatment was higher than in other treatments; at the end of the larval period the difference was twofold. In group B there were no clear effects of acid rain on the susceptibility of larvae to virus. The study yielded the following new information: (1) the effect of prolonged acid rain treatment on reducing the efficacy of virus on young larvae was more distinct than in a previous study with shorter exposure to acid rain, and the difference was maintained to the end of larval period; (2) the susceptibility of older larvae to virus was not affected by acid rain treatments; (3) pH inside the needles did not explain the larval mortality caused by virus. 相似文献
965.
《Cell》2022,185(20):3789-3806.e17
966.
《Free radical research》2013,47(10):804-810
AbstractOxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide-generating nicotinamide adenine dinucleotide phosphate-oxidase 2 (NOX2, encoded by the CYBB gene) and the antioxidant enzyme glutathione peroxidase 4 (GPX4) play opposing roles in the balance of cellular redox status. In the present study, we investigated associations of single nucleotide polymorphisms (SNPs) in the regulatory regions of CYBB and GPX4 with kidney disease in patients with type 1 diabetes. Two functional SNPs, rs6610650 (CYBB promoter region, chromosome X) and rs713041 (GPX4 3'untranslated region, chromosome 19), were genotyped in 451 patients with type 1 diabetes from a Brazilian cohort (diabetic nephropathy: 44.6%) and in 945 French/Belgian patients with type 1 diabetes from Genesis and GENEDIAB cohorts (diabetic nephropathy: 62.3%). The minor A-allele of CYBB rs6610650 was associated with lower estimated glomerular filtration rate (eGFR) in Brazilian women, and with the prevalence of established/advanced nephropathy in French/Belgian women (odds ratio 1.75, 95% CI 1.11–2.78, p = 0.016). The minor T-allele of GPX4 rs713041 was inversely associated with the prevalence of established/advanced nephropathy in Brazilian men (odds ratio 0.30, 95% CI 0.13–0.68, p = 0.004), and associated with higher eGFR in French/Belgian men. In conclusion, these heterogeneous results suggest that neither CYBB nor GPX4 are major genetic determinants of diabetic nephropathy, but nevertheless, they could modulate in a gender-specific manner the risk for renal disease in patients with type 1 diabetes. 相似文献
967.
Estimating null allele frequencies at a microsatellite locus in the oystercatcher (Haematopus ostralegus) 总被引:2,自引:0,他引:2
R. VAN TREUREN 《Molecular ecology》1998,7(10):1413-1417
A significant heterozygote deficiency was found for microsatellite locus 20H7 among adult breeding birds in four populations of the oystercatcher ( Haematopus ostralegus ). Genotype frequencies at seven other loci were according to Hardy–Weinberg equilibria. Deviations between observed and expected genotype numbers decreased substantially when the data were corrected based on the estimated frequency of a putative null allele at locus 20H7 . However, no null homozygotes were observed in the total sample of 378 individuals. The probability that, because of chance effects, null homozygotes were not represented in the sample ( n =230) from the most intensively studied population (Schiermonnikoog) was estimated to be less than 1%. Parent–offspring comparisons from Schiermonnikoog showed that observed genotype numbers in the offspring were in accordance with expected values based on the estimated frequency of the putative null allele in the population. Moreover, a null homozygote was observed among the nestlings. The combined results indicated that a null allele is present at locus 20H7 in oystercatchers and that the inheritance is according to normal Mendelian segregation. If the absence of null homozygotes among adult animals cannot be ascribed to statistical effects, null homozygotes may suffer a selective disadvantage during the juvenile stage. 相似文献
968.
Traditionally, population genetics focuses on the dynamics of frequencies of alleles acquired by mutations on germ-lines, because only such mutations are heritable. Typical genotyping experiments, however, use DNA from some somatic tissues such as blood, which harbors somatic mutations at the current generation in addition to germ-line mutations accumulated since the most recent common ancestor of the sample. This common practice may sometimes cause erroneous interpretations of polymorphism data, unless we properly understand the role of somatic mutations in population genetics. We here introduce a very basic theoretical framework of population genetics with somatic mutations taken into account. It is easy to imagine that somatic mutations at the current generation simply add individual-specific variations, as errors in mutation detection do. Our theory quantifies this increment under various conditions. We find that the major contribution of somatic mutations plus errors is to very rare variants, particularly to singletons. The relative contribution is markedly large when mutations are deleterious. Because negative selection also increases rare variants, it is important to distinguish the roles of these mutually confounding factors when we interpret the data, even after correcting for demography. We apply this theory to human copy number variations (CNVs), for which the composite effect of somatic mutations and errors may not be negligible. Using genome-wide CNV data, we demonstrate how the joint action of the two factors, selection and somatic mutations plus errors, shapes the observed pattern of polymorphism. 相似文献
969.
970.