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991.
Nicolás A. Rey Ademir Neves Flávia C.S. Paula Françoise V. Botelho Claus T. Pich Elene C. Pereira-Maia 《Journal of inorganic biochemistry》2009,103(10):1323-1330
We have studied the protonation equilibria of a dicopper(II) complex [Cu2(μ-OH)(C21H33ON6)](ClO4)2·H2O, (1), in aqueous solution, its interactions with DNA, its cytotoxic activity, and its uptake in tumoral cells. C21H33ON6 corresponds to the ligand 4-methyl-2,6-bis[(6-methyl-1,4-diazepan-6-yl)iminomethyl]phenol. From spectrophotometric data the following pKa values were calculated 3.27, 4.80 and 6.10. Complex 1 effectively promotes the hydrolytic cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions. The following kinetic parameters were calculated kcat of 2.73 × 10−4 s−1, KM of 1.36 × 10−4 M and catalytic efficiency of 2.01 s−1 M−1, a 2.73 × 107 fold increase in the rate of the reaction compared to the uncatalyzed hydrolysis rate of DNA. Competition assays with distamycin reveal minor groove binding. Complex 1 inhibited the growth of two tumoral cell lines, GLC4 and K562, with the IC50 values of 14.83 μM and 34.21 μM, respectively. There is a good correlation between cell growth inhibition and intracellular copper content. When treated with 1, cells accumulate approximately twice as much copper as with CuCl2. Copper-DNA adducts are formed inside cells when they are exposed to the complex. In addition, at concentrations that compound 1 inhibits tumoral cell growth it does not affect macrophage viability. These results show that complex 1 has a good therapeutic prospect. 相似文献
992.
Weigelt K Küster H Rutten T Fait A Fernie AR Miersch O Wasternack C Emery RJ Desel C Hosein F Müller M Saalbach I Weber H 《Plant physiology》2009,149(1):395-411
993.
Timothy P. Brennan John O. Woods Ahmad R. Sedaghat Janet D. Siliciano Robert F. Siliciano Claus O. Wilke 《Journal of virology》2009,83(17):8470-8481
Highly active antiretroviral therapy (HAART) can reduce human immunodeficiency virus type 1 (HIV-1) viremia to clinically undetectable levels. Despite this dramatic reduction, some virus is present in the blood. In addition, a long-lived latent reservoir for HIV-1 exists in resting memory CD4+ T cells. This reservoir is believed to be a source of the residual viremia and is the focus of eradication efforts. Here, we use two measures of population structure—analysis of molecular variance and the Slatkin-Maddison test—to demonstrate that the residual viremia is genetically distinct from proviruses in resting CD4+ T cells but that proviruses in resting and activated CD4+ T cells belong to a single population. Residual viremia is genetically distinct from proviruses in activated CD4+ T cells, monocytes, and unfractionated peripheral blood mononuclear cells. The finding that some of the residual viremia in patients on HAART stems from an unidentified cellular source other than CD4+ T cells has implications for eradication efforts.Successful treatment of human immunodeficiency virus type 1 (HIV-1) infection with highly active antiretroviral therapy (HAART) reduces free virus in the blood to levels undetectable by the most sensitive clinical assays (18, 36). However, HIV-1 persists as a latent provirus in resting, memory CD4+ T lymphocytes (6, 9, 12, 16, 48) and perhaps in other cell types (45, 52). The latent reservoir in resting CD4+ T cells represents a barrier to eradication because of its long half-life (15, 37, 40-42) and because specifically targeting and purging this reservoir is inherently difficult (8, 25, 27).In addition to the latent reservoir in resting CD4+ T cells, patients on HAART also have a low amount of free virus in the plasma, typically at levels below the limit of detection of current clinical assays (13, 19, 35, 37). Because free virus has a short half-life (20, 47), residual viremia is indicative of active virus production. The continued presence of free virus in the plasma of patients on HAART indicates either ongoing replication (10, 13, 17, 19), release of virus after reactivation of latently infected CD4+ T cells (22, 24, 31, 50), release from other cellular reservoirs (7, 45, 52), or some combination of these mechanisms. Finding the cellular source of residual viremia is important because it will identify the cells that are still capable of producing virus in patients on HAART, cells that must be targeted in any eradication effort.Detailed analysis of this residual viremia has been hindered by technical challenges involved in working with very low concentrations of virus (13, 19, 35). Recently, new insights into the nature of residual viremia have been obtained through intensive patient sampling and enhanced ultrasensitive sequencing methods (1). In a subset of patients, most of the residual viremia consisted of a small number of viral clones (1, 46) produced by a cell type severely underrepresented in the peripheral circulation (1). These unique viral clones, termed predominant plasma clones (PPCs), persist unchanged for extended periods of time (1). The persistence of PPCs indicates that in some patients there may be another major cellular source of residual viremia (1). However, PPCs were observed in a small group of patients who started HAART with very low CD4 counts, and it has been unclear whether the PPC phenomenon extends beyond this group of patients. More importantly, it has been unclear whether the residual viremia generally consists of distinct virus populations produced by different cell types.Since the HIV-1 infection in most patients is initially established by a single viral clone (23, 51), with subsequent diversification (29), the presence of genetically distinct populations of virus in a single individual can reflect entry of viruses into compartments where replication occurs with limited subsequent intercompartmental mixing (32). Sophisticated genetic tests can detect such population structure in a sample of viral sequences (4, 39, 49). Using two complementary tests of population structure (14, 43), we analyzed viral sequences from multiple sources within individual patients in order to determine whether a source other than circulating resting CD4+ T cells contributes to residual viremia and viral persistence. Our results have important clinical implications for understanding HIV-1 persistence and treatment failure and for improving eradication strategies, which are currently focusing only on the latent CD4+ T-cell reservoir. 相似文献
994.
Erik B Dam Marco Loog Claus Christiansen Inger Byrjalsen Jenny Folkesson Mads Nielsen Arish A Qazi Paola C Pettersen Patrick Garnero Morten A Karsdal 《Arthritis research & therapy》2009,11(4):R115
Introduction
At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations of biochemical and magnetic resonance imaging (MRI)-based markers provided effective diagnostic and prognostic tools for identifying subjects with high risk of progression. Specifically, we investigated aggregate cartilage longevity markers combining markers of breakdown, quantity, and quality. 相似文献995.
Claus Desler Prashanth Suravajhala May Sanderhoff Merete Rasmussen Lene Juel Rasmussen 《BMC bioinformatics》2009,10(1):289
Background
The definition of a hypothetical protein is a protein that is predicted to be expressed from an open reading frame, but for which there is no experimental evidence of translation. Hypothetical proteins constitute a substantial fraction of proteomes of human as well as of other eukaryotes. With the general belief that the majority of hypothetical proteins are the product of pseudogenes, it is essential to have a tool with the ability of pinpointing the minority of hypothetical proteins with a high probability of being expressed. 相似文献996.
Claus Kemkemer Matthias Kohn David N Cooper Lutz Froenicke Josef Högel Horst Hameister Hildegard Kehrer-Sawatzki 《BMC evolutionary biology》2009,9(1):84-24
Background
Genome comparisons have made possible the reconstruction of the eutherian ancestral karyotype but also have the potential to provide new insights into the evolutionary inter-relationship of the different eutherian orders within the mammalian phylogenetic tree. Such comparisons can additionally reveal (i) the nature of the DNA sequences present within the evolutionary breakpoint regions and (ii) whether or not the evolutionary breakpoints occur randomly across the genome. Gene synteny analysis (E-painting) not only greatly reduces the complexity of comparative genome sequence analysis but also extends its evolutionary reach. 相似文献997.
Lærke Egefjord Ledet Jens Jensen Claus Heiner Bang-Berthelsen Brønden Andreas Petersen Kamille Smidt Ole Schmitz Allan Ertman Karlsen Flemming Pociot Fabrice Chimienti Jørgen Rungby Nils E Magnusson 《BMC endocrine disorders》2009,9(1):1-10
Background
Numerous studies have reported that age-induced increased parathyroid hormone plasma levels are associated with cognitive decline and dementia. Little is known about the correlation that may exist between neurological processing speed, cognition and bone density in cases of hyperparathyroidism. Thus, we decided to determine if parathyroid hormone levels correlate to processing speed and/or bone density.Methods
The recruited subjects that met the inclusion criteria (n = 92, age-matched, age 18-90 years, mean = 58.85, SD = 15.47) were evaluated for plasma parathyroid hormone levels and these levels were statistically correlated with event-related P300 potentials. Groups were compared for age, bone density and P300 latency. One-tailed tests were used to ascertain the statistical significance of the correlations. The study groups were categorized and analyzed for differences of parathyroid hormone levels: parathyroid hormone levels <30 (n = 30, mean = 22.7 ± 5.6 SD) and PTH levels >30 (n = 62, mean = 62.4 ± 28.3 SD, p ≤ 02).Results
Patients with parathyroid hormone levels <30 showed statistically significantly less P300 latency (P300 = 332.7 ± 4.8 SE) relative to those with parathyroid hormone levels >30, which demonstrated greater P300 latency (P300 = 345.7 ± 3.6 SE, p = .02). Participants with parathyroid hormone values <30 (n = 26) were found to have statistically significantly higher bone density (M = -1.25 ± .31 SE) than those with parathyroid hormone values >30 (n = 48, M = -1.85 ± .19 SE, p = .04).Conclusion
Our findings of a statistically lower bone density and prolonged P300 in patients with high parathyroid hormone levels may suggest that increased parathyroid hormone levels coupled with prolonged P300 latency may become putative biological markers of both dementia and osteoporosis and warrant intensive investigation. 相似文献998.
999.
Claus Orendt Claudia Schmitt Chris van Liefferinge Georg Wolfram Eric de Deckere 《Biological invasions》2010,12(1):265-283
This paper reviews published knowledge on how to deal with invasive species during biological quality assessments in European
river systems for water management and assessments of ecological quality required, for example, by the European Water Frame
Work Directive. The papers studied included international papers and some standards for water assessment. An overview of the
current state of neozoa research showed that many different topics are treated, comprising biogeography and fauna records,
species replacements and effectiveness of colonisation, life cycles, competition between native and invasive species, habitat
quality and pathways of migration. Additionally, some papers have been published recently on the integration of neozoa in
index-based assessment systems. Although the decline or increase of alien species populations and the corresponding impacts
on indigenous populations were frequently observed, the mechanisms behind the invasions often remain hypothetical. In the
reviewed papers, issues such as possible reasons for coexistence, tolerances, quality of habitat or water, life history traits
and introduction of diseases were rarely covered. Few neozoa are sufficiently investigated to be categorised as indicators.
After discussing the advantages and disadvantages of inclusion or exclusion, inclusion of invaders in assessments of both
biodiversity (all species) and human impact (only species classified in their specific tolerance) is suggested. Further research
is required to (1) update and assign ecological profiles of the non-indigenous species currently and (2) assess the effects
of new invaders on native communities. 相似文献
1000.
Wendel Wohlleben Thomas Subkowski Claus Bollschweiler Bernhard von Vacano Yaqian Liu Wolfgang Schrepp Ulf Baus 《European biophysics journal : EBJ》2010,39(3):457-468
Hydrophobins are available from natural resources only in milligram amounts. BASF succeeded in a recombinant production process,
up-scaled to pilot plant production in kilogram scale. Strain and protein optimization by modulation of gene expression and
generation of fusion proteins finally leads to two class I hydrophobins called H*Protein A and H*Protein B. By analytical
ultracentrifugation, we confirm that the self-association of H*Proteins in solution is governed by their sequence, because
oligomerization is induced by the same mechanisms (pH > 6, temperature ≫ 5°C, concentration > 0.2 mg/ml) as for the well-known
native hydrophobins SC3 and HFB II. Additionally, we established the triggering of structure formation by bridging with divalent
ions and the stabilization of dimers and tetramers by monovalent ions or surfactants. This interplay with surfactants can
be exploited synergistically: The capacity for emulsification of a 300 ppm standard surfactant solution is boosted from 0
to 100% by the addition of a mere 1 ppm of our new hydrophobins, with H*Protein A and H*Protein B having specific application
profiles. This astonishing performance is rationalized by the finding that the same minute admixtures enhance significantly
the interfacial elastic modulus, thus stabilizing interfaces against coalescence and phase separation. 相似文献