全文获取类型
收费全文 | 646篇 |
免费 | 103篇 |
出版年
2020年 | 9篇 |
2017年 | 9篇 |
2016年 | 9篇 |
2015年 | 10篇 |
2014年 | 16篇 |
2013年 | 20篇 |
2012年 | 25篇 |
2011年 | 22篇 |
2010年 | 15篇 |
2009年 | 12篇 |
2008年 | 26篇 |
2007年 | 20篇 |
2006年 | 19篇 |
2005年 | 21篇 |
2004年 | 17篇 |
2003年 | 21篇 |
2002年 | 22篇 |
2001年 | 18篇 |
2000年 | 20篇 |
1999年 | 18篇 |
1998年 | 11篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1993年 | 10篇 |
1992年 | 19篇 |
1991年 | 14篇 |
1990年 | 18篇 |
1989年 | 12篇 |
1988年 | 18篇 |
1987年 | 22篇 |
1986年 | 10篇 |
1985年 | 13篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 11篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 10篇 |
1978年 | 10篇 |
1977年 | 13篇 |
1976年 | 10篇 |
1975年 | 15篇 |
1974年 | 16篇 |
1973年 | 14篇 |
1972年 | 12篇 |
1971年 | 11篇 |
1970年 | 14篇 |
1969年 | 11篇 |
1968年 | 7篇 |
1966年 | 6篇 |
排序方式: 共有749条查询结果,搜索用时 15 毫秒
91.
Carrie V. Kappel Carlos M. Duarte Keith Brander Christopher J. Brown John F. Bruno Lauren Buckley Michael T. Burrows Benjamin S. Halpern Wolfgang Kiessling Pippa Moore John M. Pandolfi Camille Parmesan Elvira S. Poloczanska David S. Schoeman William J. Sydeman Anthony J. Richardson 《Global Ecology and Biogeography》2015,24(1):64-76
92.
LaRonda L. Morford Christopher J. Bowman Diann L. Blanset Ingrid B. Bøgh Gary J. Chellman Wendy G. Halpern Gerhard F. Weinbauer Timothy P. Coogan 《Birth defects research. Part B, Developmental and reproductive toxicology》2011,92(4):359-380
Evaluation of pharmaceutical agents in children is now conducted earlier in the drug development process. An important consideration for this pediatric use is how to assess and support its safety. This article is a collaborative effort of industry toxicologists to review strategies, challenges, and current practice regarding preclinical safety evaluations supporting pediatric drug development with biopharmaceuticals. Biopharmaceuticals include a diverse group of molecular, cell‐based or gene therapeutics derived from biological sources or complex biotechnological processes. The principles of preclinical support of pediatric drug development for biopharmaceuticals are similar to those for small molecule pharmaceuticals and in general follow the same regulatory guidances outlined by the Food and Drug Administration and European Medicines Agency. However, many biopharmaceuticals are also inherently different, with limited species specificity or immunogenic potential which may impact the approach taken. This article discusses several key areas to aid in the support of pediatric clinical use, study design considerations for juvenile toxicity studies when they are needed, and current practices to support pediatric drug development based on surveys specifically targeting biopharmaceutical development. Birth Defects Res (Part B) 92:359–380, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
93.
94.
Martin NA Mount Patrick SK Estrada TE Frisk HA Rogan DT Dvorak B Halpern MD 《PloS one》2011,6(12):e27191
Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants, but its etiology remains unclear. We have previously shown that mucin 2 (Muc2) positive goblet cells are significantly decreased in NEC. We have also shown that ileal bile acids (BAs) are significantly increased during the development of this disease. Because BAs can affect mucins, we hypothesized that elevated ileal BAs contribute to decreased Muc2 in experimental NEC. The role of Muc2 in NEC was evaluated in Winnie +/+ mice, a strain that produces aberrant Muc2. Muc2 and trefoil factor 3 (Tff3) were assessed in neonatal rats subjected to the NEC protocol when bile acids were removed, and in ileal explants from newborn and older rats cultured with and without BAs. Further, the role of active transport of BAs was determined using neonatal rats given the apical sodium dependent bile acid transporter (Asbt) inhibitor SC-435 and in neonatal Asbt knockout mice subjected to the NEC protocol. Mice with aberrant Muc2 had significantly greater incidence and severity of NEC. Using both in vivo and ex vivo techniques, we determined that BAs decrease Muc2 positive cells in neonatal but not older ileum. However, Tff3 positive cells are not decreased by BAs. In addition, active transport of BAs is required for BAs to decrease Muc2 in immature ileum. These data show that functional Muc2 plays a critical role in the prevention of NEC and BAs can potentiate the decreased Muc2 in disease development. Further, BAs have a more profound effect on Muc2 in immature versus older ileum, which may explain at least in part why NEC occurs almost exclusively in premature infants. 相似文献
95.
96.
97.
Identifications (IDs) of paired retronasal and orthonasal odorants were studied, with stimuli limited to air phase. Odorants were liquid extracts of plant materials, sold as food flavorings, matched by each subject both for retronasal-only and orthonasal-only air phase intensities and then learned to 100% correct veridical name retronasal-only and orthonasal-only IDs. Subjects were tested for ID of (a) retronasal-only and orthonasal-only odorants, (b) homogeneously paired odorant (the same odorant in retronasal and orthonasal locations), and (c) heterogeneously paired odorants (different odorants in retronasal and orthonasal locations). Paired odorants were presented in two different sequences: retronasal location odorant smelled first or orthonasal location odorant smelled first. IDs were reported after odorants were removed. Results were as follows: (a) no significant differences between correct ID of odorants when in retronasal-only versus orthonasal-only locations, although percent correct IDs were lower for half the retronasal-only location odorants; (b) correct ID of a homogeneously paired odorant equaled or exceeded its unpaired ID, with two successive, identical IDs reported on the majority of its trials; (c) with heterogeneous pairs, for all odorants when in the orthonasal location of a pair, correct ID occurred less often than when these odorants were presented orthonasal-only, but for odorants in the retronasal location, correct ID equaled or exceeded retronasal-only correct ID; and (d) perceived order of presentation of heterogeneous pairs was the reverse of the physically presented sequence for both retronasal-first and orthonasal-first conditions. The heterogeneous odorant ID outcome supports the concept that processing of retronasal and orthonasal odorants differ, and the perceived reversal of the presented sequence is in agreement with the importance of recency in odorant memory. 相似文献
98.
Gamse JT Kuan YS Macurak M Brösamle C Thisse B Thisse C Halpern ME 《Development (Cambridge, England)》2005,132(21):4869-4881
The zebrafish epithalamus, consisting of the pineal complex and flanking dorsal habenular nuclei, provides a valuable model for exploring how left-right differences could arise in the vertebrate brain. The parapineal lies to the left of the pineal and the left habenula is larger, has expanded dense neuropil, and distinct patterns of gene expression from the right habenula. Under the influence of Nodal signaling, positioning of the parapineal sets the direction of habenular asymmetry and thereby determines the left-right origin of habenular projections onto the midbrain target, the interpeduncular nucleus (IPN). In zebrafish with parapineal reversal, neurons from the left habenula project to a more limited ventral IPN region where right habenular axons would normally project. Conversely, efferents from the right habenula adopt a more extensive dorsoventral IPN projection pattern typical of left habenular neurons. Three members of the leftover-related KCTD (potassium channel tetramerization domain containing) gene family are expressed differently by the left and right habenula, in patterns that define asymmetric subnuclei. Molecular asymmetry extends to protein levels in habenular efferents, providing additional evidence that left and right axons terminate within different dorsoventral regions of the midbrain target. Laser-mediated ablation of the parapineal disrupts habenular asymmetry and consequently alters the dorsoventral distribution of innervating axons. The results demonstrate that laterality of the dorsal forebrain influences the formation of midbrain connections and their molecular properties. 相似文献
99.
Vibrio cholerae is a waterborne bacterium native to the aquatic environment. There are over 200 known serogroups yet only two cause cholera pandemics in humans. Direct contact of human sewage with drinking water, sea-born currents and marine transportation, represent modes of dissemination of the bacteria and thus the disease. The simultaneous cholera outbreaks that occur sometimes in distant localities within continental landmasses are puzzling. Here we present evidence that flying, non-biting midges (Diptera; Chironomidae), collected in the air, carry viable non-O1 non-O139 serogroups of V. cholerae. The association of V. cholerae with chironomid egg masses, which serve as a V. cholerae reservoir, was further confirmed. In simulated field experiments, we recorded the transfer of environmental V. cholerae by adult midges from the aquatic environment into bacteria-free water-pools. In laboratory experiments, flying adult midges that emerged from V. cholerae (O1 or O139) contaminated water transferred the green fluorescent protein (GFP)-tagged pathogenic bacteria from one laboratory flasks to another. Our findings show that aerial transfer by flying chironomids may play a role in the dissemination of V. cholerae in nature. 相似文献
100.
Khateeb S Flusser H Ofir R Shelef I Narkis G Vardi G Shorer Z Levy R Galil A Elbedour K Birk OS 《American journal of human genetics》2006,79(5):942-948
Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive progressive neurodegenerative disease that presents within the first 2 years of life and culminates in death by age 10 years. Affected individuals from two unrelated Bedouin Israeli kindreds were studied. Brain imaging demonstrated diffuse cerebellar atrophy and abnormal iron deposition in the medial and lateral globus pallidum. Progressive white-matter disease and reduction of the N-acetyl aspartate : chromium ratio were evident on magnetic resonance spectroscopy, suggesting loss of myelination. The clinical and radiological diagnosis of INAD was verified by sural nerve biopsy. The disease gene was mapped to a 1.17-Mb locus on chromosome 22q13.1 (LOD score 4.7 at recombination fraction 0 for SNP rs139897), and an underlying mutation common to both affected families was identified in PLA2G6, the gene encoding phospholipase A2 group VI (cytosolic, calcium-independent). These findings highlight a role of phospholipase in neurodegenerative disorders. 相似文献