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   2549篇
  免费   235篇
  国内免费   1篇
  2023年   11篇
  2022年   27篇
  2021年   47篇
  2020年   23篇
  2019年   36篇
  2018年   52篇
  2017年   41篇
  2016年   57篇
  2015年   77篇
  2014年   106篇
  2013年   135篇
  2012年   186篇
  2011年   193篇
  2010年   106篇
  2009年   106篇
  2008年   159篇
  2007年   167篇
  2006年   132篇
  2005年   114篇
  2004年   113篇
  2003年   113篇
  2002年   118篇
  2001年   39篇
  2000年   26篇
  1999年   31篇
  1998年   24篇
  1997年   27篇
  1996年   19篇
  1995年   30篇
  1994年   11篇
  1993年   10篇
  1992年   33篇
  1991年   26篇
  1990年   19篇
  1989年   36篇
  1988年   23篇
  1987年   26篇
  1986年   22篇
  1985年   26篇
  1984年   14篇
  1982年   17篇
  1981年   13篇
  1979年   11篇
  1977年   10篇
  1975年   9篇
  1974年   16篇
  1973年   9篇
  1972年   10篇
  1971年   10篇
  1969年   9篇
排序方式: 共有2785条查询结果,搜索用时 31 毫秒
871.
The multiple species de novo gene prediction problem can be stated as follows: given an alignment of genomic sequences from two or more organisms, predict the location and structure of all protein-coding genes in one or more of the sequences. Here, we present a new system, N-SCAN (a.k.a. TWINSCAN 3.0), for addressing this problem. N-SCAN can model the phylogenetic relationships between the aligned genome sequences, context dependent substitution rates, and insertions and deletions. An implementation of N-SCAN was created and used to generate predictions for the entire human genome and the genome of the fruit fly Drosophila melanogaster. Analyses of the predictions reveal that N-SCAN's accuracy in both human and fly exceeds that of all previously published whole-genome de novo gene predictors.  相似文献   
872.
Functional impairment of HIV-specific CD4(+) T cells during chronic HIV infection is closely linked to viral replication and thought to be due to T cell exhaustion. Programmed death 1 (PD-1) has been linked to T cell dysfunction in chronic viral infections, and blockade of the PD-1 pathway restores HIV-specific CD4(+) and CD8(+) T cell function in HIV infection. This study extends those findings by directly examining PD-1 expression on virus-specific CD4(+) T cells. To investigate the role of PD-1 in HIV-associated CD4(+) T cell dysfunction, we measured PD-1 expression on blood and lymph node T cells from HIV-infected subjects with chronic disease. PD-1 expression was significantly higher on IFN-gamma-producing HIV-specific CD4(+) T cells compared with total or CMV-specific CD4(+) T cells in untreated HIV-infected subjects (p = 0.0001 and p < 0.0001, respectively). PD-1 expression on HIV-specific CD4(+) T cells from subjects receiving antiretroviral therapy was significantly reduced (p = 0.007), and there was a direct correlation between PD-1 expression on HIV-specific CD4(+) T cells and plasma viral load (r = 0.71; p = 0.005). PD-1 expression was significantly higher on HIV-specific T cells in the lymph node, the main site of HIV replication, compared with those in the blood (p = 0.0078). Thus, PD-1 expression on HIV-specific CD4(+) T cells is driven by persistent HIV replication, providing a potential target for enhancing the functional capacity of HIV-specific CD4(+) T cells.  相似文献   
873.
874.
Through a multi-university and interdisciplinary project we have involved undergraduate biology and computer science research students in the functional annotation of maize genes and the analysis of their microarray expression patterns. We have created a database to house the results of our functional annotation of >4400 genes identified as being differentially regulated in the maize shoot apical meristem (SAM). This database is located at http://sam.truman.edu and is now available for public use. The undergraduate students involved in constructing this unique SAM database received hands-on training in an intellectually challenging environment, which has prepared them for graduate and professional careers in biological sciences. We describe our experiences with this project as a model for effective research-based teaching of undergraduate biology and computer science students, as well as for a rich professional development experience for faculty at predominantly undergraduate institutions.  相似文献   
875.
Degradation and destruction of valuable spawning and rearing habitat due to anthropogenic changes (e.g., flow modification and channelisation) is known to have dramatic impacts on fish populations. To compensate for habitat losses due to hydropower development, an artificial fluvial habitat channel (‘Compensation Creek’) was constructed in south-central Newfoundland, Canada. The creek was designed to include appropriate habitat features for the two dominant salmonid fish species, landlocked Atlantic salmon (Salmo salar L.) and brook charr (Salvenius fontinalis Mitchell). The study examines the habitat use of landlocked Atlantic salmon and brook charr in the Compensation Creek using electromyogram (EMG) radio telemetry. Ten landlocked Atlantic salmon and eight brook charr were captured and tagged with EMG transmitters. In laboratory swimming experiments, the EMG values were calibrated against swimming speed. Fish were then released in the Compensation Creek and tracked on a daily basis. The results show that (1) during residence in the creek, both species used preferentially the habitat features designed to match their rearing habitat preferences, and (2) swimming speed did not vary among habitat types for either species.  相似文献   
876.
Class-A scavenger receptors (SR-A) are cellular pattern recognition receptors that bind and traffic a variety of endogenous and microbial ligands. However, despite an emerging role for SR-A as a contributor to the innate immune system, little is known of the regulation or function of SR-A on dendritic cells (DCs). Here we show that SR-A expression is upregulated during murine DC differentiation and that SR-A expression levels correlate with the expression of the murine DC marker CD11c. Using bone marrow-derived DCs (BMDCs) from SR-A knockout (SR-A(-/-)) mice, we investigated the contribution of SR-A to BMDC particulate phagocytosis. Functional analyses demonstrated that SR-A is a critical phagocytic receptor for BMDC internalization of the gram-negative bacteria E. coli. SR-A(-/-) BMDCs were impaired in their ability to phagocytose bacteria, and this deficit varied with the bacteria:BMDC cell ratio. Microscopic and biochemical analyses revealed that SR-A is broadly distributed on the surface of BMDCs and is not physically associated with lipid rafts. However, cholesterol depletion demonstrated dependence of SR-A-mediated phagocytosis upon lipid rafts. These data demonstrate a functional contribution for SR-A in the BMDC phagocytic pathway.  相似文献   
877.
878.
Selective incorporation of polyanionic molecules into hamster prions   总被引:3,自引:0,他引:3  
The central pathogenic event of prion disease is the conformational conversion of a host protein, PrPC, into a pathogenic isoform, PrPSc. We previously showed that the protein misfolding cyclic amplification (PMCA) technique can be used to form infectious prion molecules de novo from purified native PrPC molecules in an autocatalytic process requiring accessory polyanions (Deleault, N. R., Harris, B. T., Rees, J. R., and Supattapone, S. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 9741-9746). Here we investigated the molecular mechanism by which polyanionic molecules facilitate infectious prion formation in vitro.Ina PMCA reaction lacking PrPSc template seed, synthetic polyA RNA molecules induce hamster HaPrPC to adopt a protease-sensitive, detergent-insoluble conformation reactive against antibodies specific for PrPSc. During PMCA, labeled nucleic acids form nuclease-resistant complexes with HaPrP molecules. Strikingly, purified HaPrPC molecules subjected to PMCA selectively incorporate an approximately 1-2.5-kb subset of [32P]polyA RNA molecules from a heterogeneous mixture ranging in size from approximately 0.1 to >6 kb. Neuropathological analysis of scrapie-infected hamsters using the fluorescent dye acridine orange revealed that RNA molecules co-localize with large extracellular HaPrP aggregates. These findings suggest that polyanionic molecules such as RNA may become selectively incorporated into stable complexes with PrP molecules during the formation of native hamster prions.  相似文献   
879.
Symmetry-based resistance as a novel means of lower limb rehabilitation   总被引:1,自引:0,他引:1  
Robotic devices hold much promise for use as rehabilitation aids but their success depends on identifying effective strategies for controlling human-robot interaction forces. We developed a robotic device to test a novel method of controlling interaction forces with the intent of improving force symmetry in the limbs. Users perform lower limb extensions against a computer-controlled resistive load. The control software increases resistance above baseline in proportion to lower limb force asymmetry (balance between left and right limb forces). As a preliminary trial to test the device and controller, we conducted two experiments on neurologically intact subjects. In experiment 1, one group of subjects received symmetry-based resistance while performing lower limb extensions (n=10). A control group performed the same movements with constant resistance (n=10). The symmetry-based resistance group improved lower limb symmetry during training (ANOVA, p<0.05), whereas the control subjects did not. In experiment 2, subjects (n=10) successfully used symmetry-based resistance to alter their lower limb force production towards a target asymmetry (ANOVA, p<0.05). These studies suggest that symmetry-based resistance may hold rehabilitation benefits after orthopedic or neurological injury. Specifically, performing strength training therapy with this controller may allow hemiparetic individuals to focus better on increasing strength and neuromuscular recruitment in their paretic limb while experiencing symmetric limb forces.  相似文献   
880.
In a study of wolf pup survival, intraperitoneal radio transmitters were surgically implanted in 53 (27 male and 26 female) 3.5- to 8-wk-old Eastern wolf (Canis lycaon) pups at den sites in Algonquin Provincial Park, Ontario, Canada, over two whelping seasons (2004 and 2005). Pups were manually removed from dens and initially injected with butorphanol at a dosage of 0.1 mg/kg for sedation and intra-operative analgesia. Anesthesia was induced and maintained with 3% sevoflurane in oxygen via a face mask. Meloxicam (0.3 mg/kg intramuscularly) was given to provide additional analgesia. All surgeries were completed without complications, and pups were readily accepted back into the packs. No postoperative complications were identified, but two pups from a single litter drowned as a result of being moved by the pack to a flooded den following the surgery. In five pups necropsied following natural deaths, transmitters were found lying free within the peritoneal cavity, and there was no evidence of infection at the surgical site or peritonitis. Inhalation anesthesia provided extremely rapid induction (1 min) and recovery (<3 min) and was completely controllable with no residual anesthetic effects. The equipment for inhalation anesthesia was readily portable in field packs, and it has considerable advantages over injectable drugs for small and very young animals such as wolf pups. The utility of the procedure is demonstrated by the minimal effect it had on subsequent pup survival, the rapid recovery of pups following surgery, and the lack of long-term complications as determined by necropsies of pups following natural deaths.  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