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921.
Richmond M Pasupula RR Kansara SG Autery JP Monk BM Sukhodolets MV 《Biochemistry》2011,50(12):2298-2312
In this work, we describe RapA-dependent polyadenylation of model RNA substrates and endogenous, RNA polymerase-associated nucleic acid fragments. We demonstrate that the Escherichia coli RNA polymerase obtained through the classic purification procedure carries endogenous RNA oligonucleotides, which, in the presence of ATP, are polyriboadenylated in a RapA-dependent manner by an accessory poly(rA) polymerase. RNA polymerase isolated from poly(A) polymerase- (PAP-) and polynucleotide phosphorylase- (PNP-) deficient E. coli strain lacks accessory (rA)(n)-synthetic activity. Experiments with reconstituted RNA polymerase-PAP and RNA polymerase-PNP mixtures suggest that RapA enables the polyadenylation by PAP of RNA polymerase-associated RNA. Mutations disrupting RapA's ATP-hydrolytic function disrupt RapA-dependent polyadenylation, and the rapA(-)E. coli strain displays a measurable reduction in RNA polyadenylation. RapA-dependent polyadenylation can also be modulated by mutations in the section of RapA's SWI/SNF domain linked to interaction with single-stranded nucleic acid. We have developed enzymatic assays in which model, synthetic RNAs are polyriboadenylated in a RapA-dependent manner. Taken together, our results are consistent with RapA acting as an RNA polymerase-associated, ATP-dependent RNA translocase. Our work further links RapA to RNA remodeling and provides new mechanistic insights into the functional interaction between RNA polymerase and RapA. 相似文献
922.
Vaideeswaran Sivaswamy Maxim I. Boyanov Brent M. Peyton Sridhar Viamajala Robin Gerlach William A. Apel Rajesh K. Sani Alice Dohnalkova Kenneth M. Kemner Thomas Borch 《Biotechnology and bioengineering》2011,108(2):264-276
Removal of hexavalent uranium (U(VI)) from aqueous solution was studied using a Gram‐positive facultative anaerobe, Cellulomonas sp. strain ES6, under anaerobic, non‐growth conditions in bicarbonate and PIPES buffers. Inorganic phosphate was released by cells during the experiments providing ligands for formation of insoluble U(VI) phosphates. Phosphate release was most probably the result of anaerobic hydrolysis of intracellular polyphosphates accumulated by ES6 during aerobic growth. Microbial reduction of U(VI) to U(IV) was also observed. However, the relative magnitudes of U(VI) removal by abiotic (phosphate‐based) precipitation and microbial reduction depended on the buffer chemistry. In bicarbonate buffer, X‐ray absorption fine structure (XAFS) spectroscopy showed that U in the solid phase was present primarily as a non‐uraninite U(IV) phase, whereas in PIPES buffer, U precipitates consisted primarily of U(VI)‐phosphate. In both bicarbonate and PIPES buffer, net release of cellular phosphate was measured to be lower than that observed in U‐free controls suggesting simultaneous precipitation of U and PO. In PIPES, U(VI) phosphates formed a significant portion of U precipitates and mass balance estimates of U and P along with XAFS data corroborate this hypothesis. High‐resolution transmission electron microscopy (HR‐TEM) and energy dispersive X‐ray spectroscopy (EDS) of samples from PIPES treatments indeed showed both extracellular and intracellular accumulation of U solids with nanometer sized lath structures that contained U and P. In bicarbonate, however, more phosphate was removed than required to stoichiometrically balance the U(VI)/U(IV) fraction determined by XAFS, suggesting that U(IV) precipitated together with phosphate in this system. When anthraquinone‐2,6‐disulfonate (AQDS), a known electron shuttle, was added to the experimental reactors, the dominant removal mechanism in both buffers was reduction to a non‐uraninite U(IV) phase. Uranium immobilization by abiotic precipitation or microbial reduction has been extensively reported; however, the present work suggests that strain ES6 can remove U(VI) from solution simultaneously through precipitation with phosphate ligands and microbial reduction, depending on the environmental conditions. Cellulomonadaceae are environmentally relevant subsurface bacteria and here, for the first time, the presence of multiple U immobilization mechanisms within one organism is reported using Cellulomonas sp. strain ES6. Biotechnol. Bioeng. 2011;108: 264–276. © 2010 Wiley Periodicals, Inc. 相似文献
923.
Brent A. Coull Seokho Lee Glen McGee Justin Manjourides Murray A. Mittleman Gregory A. Wellenius 《Biometrics》2020,76(3):963-972
Epidemiologic studies of the short-term effects of ambient particulate matter (PM) on the risk of acute cardiovascular or cerebrovascular events often use data from administrative databases in which only the date of hospitalization is known. A common study design for analyzing such data is the case-crossover design, in which exposure at a time when a patient experiences an event is compared to exposure at times when the patient did not experience an event within a case-control paradigm. However, the time of true event onset may precede hospitalization by hours or days, which can yield attenuated effect estimates. In this article, we consider a marginal likelihood estimator, a regression calibration estimator, and a conditional score estimator, as well as parametric bootstrap versions of each, to correct for this bias. All considered approaches require validation data on the distribution of the delay times. We compare the performance of the approaches in realistic scenarios via simulation, and apply the methods to analyze data from a Boston-area study of the association between ambient air pollution and acute stroke onset. Based on both simulation and the case study, we conclude that a two-stage regression calibration estimator with a parametric bootstrap bias correction is an effective method for correcting bias in health effect estimates arising from delayed onset in a case-crossover study. 相似文献
924.
Ross Vander Vorste Mariska Obedzinski Sarah Nossaman Pierce Stephanie M. Carlson Theodore E. Grantham 《Global Change Biology》2020,26(7):3834-3845
Recent droughts raise global concern over potential biodiversity loss and mitigating impacts to vulnerable species has become a management priority. However, drought impacts on populations are difficult to predict, in part, because habitat refuges can buffer organisms from harsh environmental conditions. In a global change context, more extreme droughts may turn previously suitable habitats into ecological traps, where vulnerable species can no longer persist. Here, we explore the impacts of California's recent record‐breaking drought on endangered juvenile Coho salmon. We estimated the variability of cumulative salmon survival using mark–recapture of nearly 20,000 tagged fish in intermittent stream pools during a 7‐year period encompassing drought and non‐drought conditions. We then determined the relative importance of physical habitat, streamflow, precipitation, landscape, and biological characteristics that may limit survival during drought. Our most striking result was an increase in the number of pools with reduced or zero survival during drought years and a coincident increase in spatial variability in survival among study reaches. In nearly half of the stream pools, salmon survival during drought was similar to mean survival of pools assessed during non‐drought years, indicating some pools had remarkable resistance (ability to withstand disturbance) to extreme drought. Lower survival was most attributable to longer duration of disconnection between upstream and downstream habitats, a consequence of increasing drought severity. Our results not only suggest that many pools sustain juvenile salmon in non‐drought years transition into ecological traps during drought but also highlight that some pools serve as refuges even under extreme drought conditions. Projected increases in drought severity that lead to longer droughts and greater habitat fragmentation could transform an increasing proportion of suitable habitats into ecological traps. Predicting future impacts of drought on Coho salmon and other sensitive species will require identification and protection of drought refuges and management strategies that prevent further habitat fragmentation. 相似文献
925.
Brent M. Horton Thomas B. Ryder Ignacio T. Moore Christopher N. Balakrishnan 《Genes, Brain & Behavior》2020,19(1)
The vertebrate basal forebrain and midbrain contain a set of interconnected nuclei that control social behavior. Conserved anatomical structures and functions of these nuclei have now been documented among fish, amphibians, reptiles, birds and mammals, and these brain regions have come to be known as the vertebrate social behavior network (SBN). While it is known that nuclei (nodes) of the SBN are rich in steroid and neuropeptide activity linked to behavior, simultaneous variation in the expression of neuroendocrine genes among several SBN nuclei has not yet been described in detail. In this study, we use RNA‐seq to profile gene expression across seven brain regions representing five nodes of the vertebrate SBN in a passerine bird, the wire‐tailed manakin Pipra filicauda. Using weighted gene co‐expression network analysis, we reconstructed sets of coregulated genes, showing striking patterns of variation in neuroendocrine gene expression across the SBN. We describe regional variation in gene networks comprising a broad set of hormone receptors, neuropeptides, steroidogenic enzymes, catecholamines and other neuroendocrine signaling molecules. Our findings show heterogeneous patterns of brain gene expression across nodes of the avian SBN and provide a foundation for future analyses of how the regulation of gene networks may mediate social behavior. These results highlight the importance of region‐specific sampling in studies of the mechanisms of behavior. 相似文献
926.
Kapeliotis Markos Gavrila Laic Rebeca Alejandra Peñas Alvaro Jorge Vander Sloten Jos Vanden Berghe Pieter Famaey Nele Depreitere Bart 《Biomechanics and modeling in mechanobiology》2020,19(6):2455-2489
Biomechanics and Modeling in Mechanobiology - Bridging veins (BVs) drain the blood from the cerebral cortex into dural sinuses. BVs have one end attached to the brain and the other to the superior... 相似文献
927.
Austin Y. Shull Megan L. Clendenning Sampa Ghoshal-Gupta Christopher L. Farrell Hima V. Vangapandu Larry Dudas Brent J. Wilkerson Phillip J. Buckhaults 《PloS one》2013,8(3)
Background
The Cub and Sushi Multiple Domains 1 (CSMD1) gene, located on the short arm of chromosome 8, codes for a type I transmembrane protein whose function is currently unknown. CSMD1 expression is frequently lost in many epithelial cancers. Our goal was to characterize the relationships between CSMD1 somatic mutations, allele imbalance, DNA methylation, and the clinical characteristics in colorectal cancer patients.Methods
We sequenced the CSMD1 coding regions in 54 colorectal tumors using the 454FLX pyrosequencing platform to interrogate 72 amplicons covering the entire coding sequence. We used heterozygous SNP allele ratios at multiple CSMD1 loci to determine allelic balance and infer loss of heterozygosity. Finally, we performed methylation-specific PCR on 76 colorectal tumors to determine DNA methylation status for CSMD1 and known methylation targets ALX4, RUNX3, NEUROG1, and CDKN2A.Results
Using 454FLX sequencing and confirming with Sanger sequencing, 16 CSMD1 somatic mutations were identified in 6 of the 54 colorectal tumors (11%). The nonsynonymous to synonymous mutation ratio of the 16 somatic mutations was 15∶1, a ratio significantly higher than the expected 2∶1 ratio (p = 0.014). This ratio indicates a presence of positive selection for mutations in the CSMD1 protein sequence. CSMD1 allelic imbalance was present in 19 of 37 informative cases (56%). Patients with allelic imbalance and CSMD1 mutations were significantly younger (average age, 41 years) than those without somatic mutations (average age, 68 years). The majority of tumors were methylated at one or more CpG loci within the CSMD1 coding sequence, and CSMD1 methylation significantly correlated with two known methylation targets ALX4 and RUNX3. C:G>T:A substitutions were significantly overrepresented (47%), suggesting extensive cytosine methylation predisposing to somatic mutations.Conclusions
Deep amplicon sequencing and methylation-specific PCR reveal that CSMD1 alterations can correlate with earlier clinical presentation in colorectal tumors, thus further implicating CSMD1 as a tumor suppressor gene. 相似文献928.
Objectives
We examined whether a sugary drink limit would still be effective if larger-sized drinks were converted into bundles of smaller-sized drinks.Methods
In a behavioral simulation, participants were offered varying food and drink menus. One menu offered 16 oz, 24 oz, or 32 oz drinks for sale. A second menu offered 16 oz drinks, a bundle of two 12 oz drinks, or a bundle of two 16 oz drinks. A third menu offered only 16 oz drinks for sale. The method involved repeated elicitation of choices, and the instructions did not mention a limit on drink size.Results
Participants bought significantly more ounces of soda with bundles than with varying-sized drinks. Total business revenue was also higher when bundles rather than only small-sized drinks were sold.Conclusions
Our research suggests that businesses have a strong incentive to offer bundles of soda when drink size is limited. Restricting larger-sized drinks may have the unintended consequence of increasing soda consumption rather than decreasing it. 相似文献929.
Jian Hua Qi Quteba Ebrahem Mariya Ali Alecia Cutler Brent Bell Nicholas Prayson Jonathan Sears Vera Knauper Gillian Murphy Bela Anand-Apte 《PloS one》2013,8(3)
Tissue inhibitors of metalloproteinases (TIMPs) while originally characterized as inhibitors of matrix metalloproteinases (MMPs) have recently been shown to have a wide range of functions that are independent of their MMP inhibitory properties. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a potent inhibitor of VEGF-mediated angiogenesis and neovascularization through its ability to block the binding of VEGF to its receptor VEGFR-2. To identify and characterize the anti-angiogenic domain of TIMP-3, structure function analyses and synthetic peptide studies were performed using VEGF-mediated receptor binding, signaling, migration and proliferation. In addition, the ability of TIMP-3 peptides to inhibit CNV in a mouse model was evaluated. We demonstrate that the anti-angiogenic property resides in the COOH-terminal domain of TIMP-3 protein which can block the binding of VEGF specifically to its receptor VEGFR-2, but not to VEGFR-1 similar to the full-length wild-type protein. Synthetic peptides corresponding to putative loop 6 and tail region of TIMP-3 have anti-angiogenic properties as determined by inhibition of VEGF binding to VEGFR-2, VEGF-induced phosphorylation of VEGFR-2 and downstream signaling pathways as well as endothelial cell proliferation and migration in response to VEGF. In addition, we show that intravitreal administration of TIMP-3 peptide could inhibit the size of laser-induced choroidal neovascularization lesions in mice. Thus, we have identified TIMP-3 peptides to be efficient inhibitors of angiogenesis and have a potential to be used therapeutically in diseases with increased neovascularization. 相似文献
930.
Katherine T. Mills L. Lee Hamm A. Brent Alper Chad Miller Alhakam Hudaihed Saravanan Balamuthusamy Chung-Shiuan Chen Yanxi Liu Joseph Tarsia Nader Rifai Myra Kleinpeter Jiang He Jing Chen 《PloS one》2013,8(10)