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   2320篇
  免费   180篇
  国内免费   6篇
  2506篇
  2022年   24篇
  2021年   35篇
  2020年   23篇
  2019年   30篇
  2018年   45篇
  2017年   33篇
  2016年   46篇
  2015年   79篇
  2014年   99篇
  2013年   130篇
  2012年   209篇
  2011年   162篇
  2010年   96篇
  2009年   99篇
  2008年   140篇
  2007年   155篇
  2006年   149篇
  2005年   117篇
  2004年   143篇
  2003年   108篇
  2002年   93篇
  2001年   29篇
  2000年   18篇
  1999年   21篇
  1998年   32篇
  1997年   17篇
  1996年   15篇
  1995年   19篇
  1994年   25篇
  1993年   25篇
  1992年   17篇
  1991年   20篇
  1990年   18篇
  1989年   11篇
  1988年   14篇
  1987年   12篇
  1986年   11篇
  1985年   9篇
  1984年   10篇
  1983年   11篇
  1982年   16篇
  1980年   11篇
  1979年   6篇
  1978年   9篇
  1977年   9篇
  1974年   10篇
  1973年   10篇
  1971年   7篇
  1970年   6篇
  1967年   7篇
排序方式: 共有2506条查询结果,搜索用时 15 毫秒
21.
The watershed of the Altamaha River, Georgia, is one of the largest in the southeastern U.S., draining 36,718 km2 (including parts of metro Atlanta). We calculated both nitrogen (fertilizer, net food and feed import, atmospheric deposition, and biological N fixation in agricultural and forest lands) and phosphorus (fertilizer and net food and feed import) inputs to the watershed for 6 time points between 1954 and 2002. Total nitrogen inputs rose from 1,952 kg N km−2 yr−1 in 1954 to a peak of 3,593 kg N km−2 yr−1 in 1982 and then declined to 2,582 kg N km−2 yr−1 by 2002. Phosphorus inputs rose from 409 kg P km−2 yr−1 in 1954 to 532 kg P km−2 yr−1 in 1974 before declining to 412 kg P km−2 yr−1 in 2002. Fertilizer tended to be the most important input of both N and P to the watershed, although net food and feed import increased in importance over time and was the dominant source of N input by 2002. When considered on an individual basis, fertilizer input tended to be highest in the middle portions of the watershed (Little and Lower Ocmulgee and Lower Oconee sub-watersheds) whereas net food and feed imports were highest in the upper reaches (Upper Oconee and Upper Ocmulgee sub-watersheds). Although the overall trend in recent years has been towards decreases in both N and P inputs, these trends may be offset due to continuing increases in animal and human populations.  相似文献   
22.
A model of globin evolution   总被引:1,自引:0,他引:1  
Putative globins have been identified in 426 bacterial, 32 Archaeal and 67 eukaryote genomes. Among these sequences are the hitherto unsuspected presence of single domain sensor globins within Bacteria, Fungi, and a Euryarchaeote. Bayesian phylogenetic trees suggest that their occurrence in the latter two groups could be the result of lateral gene transfer from Bacteria. Iterated psiblast searches based on groups of globin sequences indicate that bacterial flavohemoglobins are closer to metazoan globins than to the other two lineages, the 2-over-2 globins and the globin-coupled sensors. Since Bacteria is the only kingdom to have all the subgroups of the three globin lineages, we propose a working model of globin evolution based on the assumption that all three lineages originated and evolved only in Bacteria. Although the 2-over-2 globins and the globin-coupled sensors recognize flavohemoglobins, there is little recognition between them. Thus, in the first stage of globin evolution, we favor a flavohemoglobin-like single domain protein as the ancestral globin. The next stage comprised the splitting off to single domain 2-over-2 and sensor-like globins, followed by the covalent addition of C-terminal domains resulting in the chimeric flavohemoglobins and globin-coupled sensors. The last stage encompassed the lateral gene transfers of some members of the three globin lineages to specific groups of Archaea and Eukaryotes.  相似文献   
23.
Coinfection with human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV) is a global problem that is more prevalent in injection drug users because they have a higher risk for acquiring both viruses. The roles of inflammatory cytokines and oxidative stress were examined in HIV-1- and HCV-coinfected human hepatic cells. Morphine (the bioactive product of heroin), HIV-1 Tat and the MN strain gp120 (gp120(MN)) proteins, and X4 HIV-1(LAI/IIIB) and R5 HIV-1(SF162) isolates were used to study the mechanisms of disease progression in HCV (JFH1)-infected Huh7.5.1 cell populations. HCV increased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release and augmented production of reactive oxygen species (ROS), nitric oxide (NO), and 3-nitrotyrosine (3-NT) in Huh7.5.1 cells. Morphine preferentially affected R5-tropic, but not X4-tropic, HIV-1 interactions with Huh7.5.1 cells. HIV-1 proteins or isolates increased cytokine release in HCV-infected cells, while adding morphine to coinfected cells caused complex imbalances, significantly disrupting cytokine secretion depending on the cytokine, morphine concentration, exposure duration, and particular pathogen involved. Production of ROS, NO, and 3-NT increased significantly in HCV- and HIV-1-coexposed cells while exposure to morphine further increased ROS. The proteasome inhibitor MG132 significantly decreased oxyradicals, cytokine levels, and HCV protein levels. Our findings indicate that hepatic inflammation is increased by combined exposure to HCV and HIV-1, that the ubiquitin-proteasome system and NF-κB contribute to key aspects of the response, and that morphine further exacerbates the disruption of host defenses. The results suggest that opioid abuse and HIV-1 coinfection each further accelerate HCV-mediated liver disease by dysregulating immune defenses.  相似文献   
24.
 Previously, transgenic mice were constructed overexpressing human insulin-like growth factor II (IGF-II) under control of the H2kb promoter. The IGF-II transgene was highly expressed in thymus and spleen, and these organs showed an increase in weight. In the current study we have analyzed the sites of IGF-II mRNA expression, the distribution of IGF-II, IGF-I, and both IGF receptors, and histomorphometrical changes in thymus and spleen. With in situ mRNA hybridization, expression of the IGF-II transgene is found with high intensity in the thymic medulla and in the white pulp/marginal zone of the spleen, whereas there were scattered positive cells in the thymic cortex and in the splenic red pulp. Hybridization was restricted to non-lymphocytic cells. Immunohistochemistry revealed intense IGF-II peptide staining with the same distribution as IGF-II mRNA. There was additional intense IGF-II staining of all elements in the splenic red pulp (including trabeculae) and diffuse, low level staining in the thymic cortex. These findings were not observed in control mice. In the thymic medulla, most IGF-II producing cells co-labelled with keratin, whereas a minor population also stained for the monocyte/macrophage marker MOMA-2. In the spleen, co-labelling of IGF-II producing cells was found with MOMA-1 (marginal zone), or with the dendritic cell marker NLDC-145 (red pulp). IGF-I and both IGF receptors were found in these organs in nearly all cell types, with a similar pattern in transgenic mice and in control animals. Histomorphometric analysis revealed a marked increase of thymus cortex size and an increased trabecular size in the spleen. This suggests that IGF-II overproduction induces local effects (auto/paracrine) in the thymic cortex, but not in the thymic medulla. Trabecular growth in the spleen most likely is a distant effect (paracrine or endocrine) of IGF-II overproduction. Accepted: 5 September 1996  相似文献   
25.
Conservation of migratory shorebirds and waterfowl presents unique challenges due to extensive historic loss of wetland habitats, and current reliance on managed landscapes for wintering and migratory passage. We developed a spatially-explicit approach to estimate potential shorebird and waterfowl densities in California by integrating mapped habitat layers and statewide bird survey data with expert-based habitat rankings. Using these density estimates as inputs, we used the Marxan site-selection program to identify priority shorebird and waterfowl areas at the ecoregional level. We identified 3.7 million ha of habitat for shorebirds and waterfowl, of which 1.4 million ha would be required to conserve 50% of wintering populations. To achieve a conservation goal of 75%, more than twice as much habitat (3.1 million ha) would be necessary. Agricultural habitats comprised a substantial portion of priority areas, especially at the 75% level, suggesting that under current management conditions, large areas of agricultural land, much of it formerly wetland, are needed to provide the habitat availability and landscape connectivity required by shorebird and waterfowl populations. These habitats were found to be largely lacking recognized conservation status in California (96% un-conserved), with only slightly higher levels of conservation for priority shorebird and waterfowl areas. Freshwater habitats, including wetlands and ponds, were also found to have low levels of conservation (67% un-conserved), although priority shorebird and waterfowl areas had somewhat higher levels of conservation than the state as a whole. Conserving migratory waterfowl and shorebirds will require a diversity of conservation strategies executed at a variety of scales. Our modeled results are complementary with other approaches and can help prioritize areas for protection, restoration and other actions. Traditional habitat protection strategies such as conservation easements and fee acquisitions may be of limited utility for protecting and managing significant areas of agricultural lands. Instead, conservation strategies focused on incentive-based programs to support wildlife friendly management practices in agricultural settings may have greater utility and conservation effectiveness.  相似文献   
26.
SUMMARY: ESS++ is a C++ implementation of a fully Bayesian variable selection approach for single and multiple response linear regression. ESS++ works well both when the number of observations is larger than the number of predictors and in the 'large p, small n' case. In the current version, ESS++ can handle several hundred observations, thousands of predictors and a few responses simultaneously. The core engine of ESS++ for the selection of relevant predictors is based on Evolutionary Monte Carlo. Our implementation is open source, allowing community-based alterations and improvements. AVAILABILITY: C++ source code and documentation including compilation instructions are available under GNU licence at http://bgx.org.uk/software/ESS.html.  相似文献   
27.
NupG from Escherichia coli is the archetype of a family of nucleoside transporters found in several eubacterial groups and has distant homologues in eukaryotes, including man. To facilitate investigation of its molecular mechanism, we developed methods for expressing an oligohistidine-tagged form of NupG both at high levels (>20% of the inner membrane protein) in E. coli and in Xenopus laevis oocytes. In E. coli recombinant NupG transported purine (adenosine) and pyrimidine (uridine) nucleosides with apparent K(m) values of approximately 20-30 microM and transport was energized primarily by the membrane potential component of the proton motive force. Competition experiments in E. coli and measurements of uptake in oocytes confirmed that NupG was a broad-specificity transporter of purine and pyrimidine nucleosides. Importantly, using high-level expression in E. coli and magic-angle spinning cross-polarization solid-state nuclear magnetic resonance, we have for the first time been able directly to measure the binding of the permeant ([1'-(13)C]uridine) to the protein and to assess its relative mobility within the binding site, under non-energized conditions. Purification of over-expressed NupG to near homogeneity by metal chelate affinity chromatography, with retention of transport function in reconstitution assays, was also achieved. Fourier transform infrared and circular dichroism spectroscopy provided further evidence that the purified protein retained its 3D conformation and was predominantly alpha-helical in nature, consistent with a proposed structure containing 12 transmembrane helices. These findings open the way to elucidating the molecular mechanism of transport in this key family of membrane transporters.  相似文献   
28.
V Sylvia  G Curtin  J Norman  J Stec  D Busbee 《Cell》1988,54(5):651-658
A low activity form of DNA polymerase alpha immunoaffinity-purified from adult-derived human fibroblasts was activated by interaction with phosphatidylinositol-4-monophosphate, while a high activity form of the enzyme did not interact with phosphatidylinositol-4-monophosphate or its derivatives. Phosphatidylinositol-4-monophosphate was apparently hydrolyzed in the presence of a highly purified low activity form of DNA polymerase alpha, effecting the release of diacylglycerol and the retention of inositol-1,4-bisphosphate by the enzyme complex. The resulting inositol-1,4-bisphosphate/protein complex exhibited increased affinity of binding to DNA template/primer and increased deoxynucleotidyltransferase activity. These data indicate that inositol-1,4-bisphosphate may function as an effector molecule in the activation of a low activity form of human DNA polymerase alpha and suggest that it may function as a second messenger during the initiation of mitosis in stimulated cells.  相似文献   
29.
We report on our initial genetic linkage studies of schizophrenia in the genetically isolated population of the Afrikaners from South Africa. A 10-cM genomewide scan was performed on 143 small families, 34 of which were informative for linkage. Using both nonparametric and parametric linkage analyses, we obtained evidence for a small number of disease loci on chromosomes 1, 9, and 13. These results suggest that few genes of substantial effect exist for schizophrenia in the Afrikaner population, consistent with our previous genealogical tracing studies. The locus on chromosome 1 reached genomewide significance levels (nonparametric LOD score of 3.30 at marker D1S1612, corresponding to an empirical P value of.012) and represents a novel susceptibility locus for schizophrenia. In addition to providing evidence for linkage for chromosome 1, we also identified a proband with a uniparental disomy (UPD) of the entire chromosome 1. This is the first time a UPD has been described in a patient with schizophrenia, lending further support to involvement of chromosome 1 in schizophrenia susceptibility in the Afrikaners.  相似文献   
30.
Altitudinal gradients are frequently used to study environmental effects on species diversity. Recent quantitative studies on Lepidoptera focussed on tropical mountain systems and often reported unimodal diversity peaks at “mid-elevations”;, a pattern also often found in other taxa. Here we used methodologically comparable, nocturnal Macrolepidoptera samples from the Swiss Alps to analyze environmental correlates of diversity. Using seasonal data (monthly samples from April to November at altitudes between 600 and 2400 m a.s.l.) allowed to decouple altitude and some climate variables for analyses. We found that the altitude–diversity pattern changes with season. In spring and autumn, diversity decreased with increasing altitude, while we found a unimodal peak of diversity at mid-elevations during summer. This excluded all hypothetical causes of diversity variation that do not allow for seasonality. Temperature was an important correlate of diversity, whereas precipitation was not. These results were separately corroborated for the two most common families (Noctuidae and Geometridae). However, diversity patterns of the two families were not particularly close, and unexplained variance of climatic explanations was substantial in all cases. The patterns of faunal overlap did not explain the unimodal diversity pattern, and we claim that we lack a generally valid explanation for this common phenomenon.  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