首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3925篇
  免费   310篇
  4235篇
  2024年   3篇
  2023年   9篇
  2022年   41篇
  2021年   68篇
  2020年   61篇
  2019年   79篇
  2018年   85篇
  2017年   80篇
  2016年   96篇
  2015年   165篇
  2014年   191篇
  2013年   262篇
  2012年   353篇
  2011年   305篇
  2010年   212篇
  2009年   203篇
  2008年   262篇
  2007年   265篇
  2006年   236篇
  2005年   192篇
  2004年   188篇
  2003年   184篇
  2002年   163篇
  2001年   62篇
  2000年   54篇
  1999年   47篇
  1998年   36篇
  1997年   32篇
  1996年   38篇
  1995年   25篇
  1994年   27篇
  1993年   22篇
  1992年   22篇
  1991年   18篇
  1990年   14篇
  1989年   11篇
  1988年   13篇
  1987年   17篇
  1986年   15篇
  1985年   16篇
  1984年   7篇
  1983年   10篇
  1982年   6篇
  1981年   10篇
  1980年   5篇
  1979年   9篇
  1978年   4篇
  1976年   3篇
  1975年   4篇
  1973年   2篇
排序方式: 共有4235条查询结果,搜索用时 15 毫秒
161.
The spatial scale at which climate and species’ occupancy data are gathered, and the resolution at which ecological models are run, can strongly influence predictions of species performance and distributions. Running model simulations at coarse rather than fine spatial resolutions, for example, can determine if a model accurately predicts the distribution of a species. The impacts of spatial scale on a model's accuracy are particularly pronounced across mountainous terrain. Understanding how these discrepancies arise requires a modelling approach in which the underlying processes that determine a species’ distribution are explicitly described. Here we use a process‐based model to explore how spatial resolution, topography and behaviour alter predictions of a species thermal niche, which in turn constrains its survival and geographic distribution. The model incorporates biophysical equations to predict the operative temperature (Te), thermal‐dependent performance and survival of a typical insect, with a complex life‐cycle, in its microclimate. We run this model with geographic data from a mountainous terrain in South Africa using climate data at three spatial resolutions. We also explore how behavioural thermoregulation affects predictions of a species performance and survival by allowing the animal to select the optimum thermal location within each coarse‐grid cell. At the regional level, coarse‐resolution models predicted lower Te at low elevations and higher Te at high elevations than models run at fine‐resolutions. These differences were more prominent on steep, north‐facing slopes. The discrepancies in Te in turn affected estimates of the species thermal niche. The modelling framework revealed how spatial resolution and topography influence predictions of species distribution models, including the potential impacts of climate change. These systematic biases must be accounted for when interpreting the outputs of future modelling studies, particularly when species distributions are predicted to shift from uniform to topographically heterogeneous landscapes.  相似文献   
162.

Background

Early diagnosis of dengue can assist patient triage and management and prevent unnecessary treatments and interventions. Commercially available assays that detect the dengue virus protein NS1 in the plasma/serum of patients offers the possibility of early and rapid diagnosis.

Methodology/Principal Findings

The sensitivity and specificity of the Pan-E Dengue Early ELISA and the Platelia™ Dengue NS1 Ag assays were compared against a reference diagnosis in 1385 patients in 6 countries in Asia and the Americas. Platelia was more sensitive (66%) than Pan-E (52%) in confirmed dengue cases. Sensitivity varied by geographic region, with both assays generally being more sensitive in patients from SE Asia than the Americas. Both kits were more sensitive for specimens collected within the first few days of illness onset relative to later time points. Pan-E and Platelia were both 100% specific in febrile patients without evidence of acute dengue. In patients with other confirmed diagnoses and healthy blood donors, Platelia was more specific (100%) than Pan-E (90%). For Platelia, when either the NS1 test or the IgM test on the acute sample was positive, the sensitivity versus the reference result was 82% in samples collected in the first four days of fever. NS1 sensitivity was not associated to disease severity (DF or DHF) in the Platelia test, whereas a trend for higher sensitivity in DHF cases was seen in the Pan-E test (however combined with lower overall sensitivity).

Conclusions/Significance

Collectively, this multi-country study suggests that the best performing NS1 assay (Platelia) had moderate sensitivity (median 64%, range 34–76%) and high specificity (100%) for the diagnosis of dengue. The poor sensitivity of the evaluated assays in some geographical regions suggests further assessments are needed. The combination of NS1 and IgM detection in samples collected in the first few days of fever increased the overall dengue diagnostic sensitivity.  相似文献   
163.
164.
The spindle checkpoint prevents anaphase onset until all the chromosomes have successfully attached to the spindle microtubules. The mechanisms by which unattached kinetochores trigger and transmit a primary signal are poorly understood, although it seems to be dependent at least in part, on the kinetochore localization of the different checkpoint components. By using protein immunodepletion and mRNA translation in Xenopus egg extracts, we have studied the hierarchic sequence and the interdependent network that governs protein recruitment at the kinetochore in the spindle checkpoint pathway. Our results show that the first regulatory step of this cascade is defined by Aurora B/INCENP complex. Aurora B/INCENP controls the activation of a second regulatory level by inducing at the kinetochore the localization of Mps1, Bub1, Bub3, and CENP-E. This localization, in turn, promotes the recruitment to the kinetochore of Mad1/Mad2, Cdc20, and the anaphase promoting complex (APC). Unlike Aurora B/INCENP, Mps1, Bub1, and CENP-E, the downstream checkpoint protein Mad1 does not regulate the kinetochore localization of either Cdc20 or APC. Similarly, Cdc20 and APC do not require each other to be localized at these chromosome structures. Thus, at the last step of the spindle checkpoint cascade, Mad1/Mad2, Cdc20, and APC are recruited at the kinetochores independently from each other.  相似文献   
165.
One of the most exciting challenges in human biology is the understanding of how our genome was constructed during evolution. Here we explore the evolutionary history of the low polymorphic human minisatellite MsH42 and its flanking sequences. We show that the evolutionary birth of MsH42 took place within an intron, early in primate lineage evolution, more than 40 MYA. Then, single base-pair changes and duplications/deletions of repeat blocks by mispairing were probably the main forces governing the generation of this minisatellite and its polymorphism throughout primate evolution. Moreover, we detected several phylogenetic footprints at both sides of MsH42. We believe that our findings will contribute to the understanding of low-variability minisatellite evolution.  相似文献   
166.
The synthesis of new analogues of 1alpha,25-dihydroxyvitamin D3 containing a carbamate function at the A-ring fragment has been described using the cross-coupling approach. The carbamate group was selectively introduced at the C-3 position by regioselective enzymatic alkoxycarbonylation of A-ring enyne 3 and subsequent treatment with ammonia, amines, amino alcohols, and amino acids. Biological studies to evaluate the potency of all five of these carbamate analogues were performed and demonstrated very low binding affinity for the vitamin D receptor compared with 1alpha,25-dihydroxyvitamin D3. Moreover, all the carbamate analogues were less active than 1alpha,25-dihydroxyvitamin D3 in inhibiting cell proliferation or stimulating cell differentiation. Of all the five analogues, the 3-O-carbamoyl-1alpha,25-(OH)2-D3 analogue 10a was the most potent one in vitro. However, all investigated carbamate analogues demonstrated lower calcemic effects in vivo than the parent compound.  相似文献   
167.
Entamoeba histolytica trophozoites are able to degrade human erythrocytes; the loss of erythrocyte cellular matrix and degradation of plasma membrane were observed, along with the decrease in the average size of digestive vacuoles. Ninety-six percent of hemoglobin ingested was hydrolyzed by trophozoites within 3h, as evidenced by electrophoresis. Accordingly, X-ray spectroscopy revealed the presence of iron inside vacuoles after erythrophagocytosis, the concentration of which decreased to control levels in a similar period. Quantification of erythrocyte digestion at the early and late periods was determined by a spectrophotometric procedure, with t(1/2)=1.67 h and 35-min for HM-1:IMSS and HK-9:NIH trophozoites, respectively. In the latter, activity was due to the combined action of intracellular enzymatic activity and exocytosis. E-64c and leupeptin totally inhibited erythrocyte digestion within a 3-h period, thereafter hydrolysis took place at lower rate. Our results suggest that erythrocyte digestion in E. histolytica proceeds in different ways in these two amebic strains, and can be blocked by proteinase inhibitors.  相似文献   
168.
It has been hypothesized that the fitness of selfed progeny must be lowered by inbreeding depression. Most research into the breeding systems of orchids shows a similar fruit set from outcrossing and self-pollination, but few studies have measured seed production and viability. In five populations of Laelia autumnalis, in central México, we studied the species reproductive system and the early costs of endogamy. We performed spontaneous self-pollination, apomixis, assisted self-pollination, cross-pollination, and exogamous pollination (using pollen from a different population) treatments of bagged flowers and measured fruit set, seed production, and germination. No fruits were produced in the apomixis and spontaneous self-pollination treatments. Reproductive success from self-pollination was lower than that from cross- and exogamous pollination and no difference was found between the latter two treatments. The ratio between self-pollination and cross-pollination success in different traits ranged from 0.80?±?0.18 (fruit set) to 0.22?±?0.13 (seeds with embryo). The latter value suggests a high endogamy costs in the production of viable seeds. The concatenated success of the different traits studied showed that the relative fitness of self-pollination was 63% lower than with cross-pollination. Laelia autumnalis is a self-compatible non-autogamous species in which the cost of endogamy occurs at seed production and cannot be compensated for at other early stages. This also occurs in other orchid species and is likely to be a general pattern.  相似文献   
169.
Summary The unpaired germarium of Dicrocoelium dendriticum contains many female germ cells at different stages of maturation and is enveloped by a fibrous basal lamina-like structure and a multilayered cytoplasmic sheath whose origins and functions are discussed. The maturation process of primary oocytes occurs completely within the prophase of the first meiotic division. It has been divided into three stages, as previously suggested for monogeneans. Stage I corresponds to oogonia and early oocytes which are located in the distal germinative area of the gonad. These cells are characterized by a high nucleo/cytoplasmic ratio and a poorly differentiated cytoplasm. Stage II corresponds to maturing oocytes grouped in the central area of the gonad and exhibiting long synaptonemal complexes and a prominent nucleolus. The main feature of cytoplasmic differentiation is the increase in the number of RER and Golgi complex which are involved in the production of small electron-dense granules. Stage III corresponds to mature oocytes located in the proximal area of the germarium near the origin of the oviduct. In this stage, the granules become regularly distributed in a monolayer in the peripheral ooplasm and make contact with the oolemma. They show a distinctive complex structure, are composed of proteins and glycoproteins and do not contain polyphenols. Their possible role as cortical granules is discussed in relation to chemical composition and previous studies on other Plathelminthes. Neither yolk globules nor glycogen are present in the oocytes.Abbreviations I oogonium and early oocyte - II growing oocyte - III mature oocyte - cg cortical granule - cs cytoplasmic sheath - db dense body - ecm extra cellular matrix - ER endoplasmic reticulum - fl fibrous extracellular layer - gc Golgi complex - m mitochondria - N nucleus - nu nucleolus - RER rough endoplasmic reticulum - sc synaptonemal complex  相似文献   
170.
Complete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. We report here that mutations in GPR179, encoding an orphan G protein receptor, underlie a form of autosomal-recessive cCSNB. The Gpr179(nob5/nob5) mouse model was initially discovered by the absence of the ERG b-wave, a component that reflects depolarizing bipolar cell (DBC) function. We performed genetic mapping, followed by next-generation sequencing of the critical region and detected a large transposon-like DNA insertion in Gpr179. The involvement of GPR179 in DBC function was confirmed in zebrafish and humans. Functional knockdown of gpr179 in zebrafish led to a marked reduction in the amplitude of the ERG b-wave. Candidate gene analysis of GPR179 in DNA extracted from patients with cCSNB identified GPR179-inactivating mutations in two patients. We developed an antibody against mouse GPR179, which robustly labeled DBC dendritic terminals in wild-type mice. This labeling colocalized with the expression of GRM6 and was absent in Gpr179(nob5/nob5) mutant mice. Our results demonstrate that GPR179 plays a critical role in DBC signal transduction and expands our understanding of the mechanisms that mediate normal rod vision.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号