全文获取类型
收费全文 | 712篇 |
免费 | 71篇 |
出版年
2022年 | 5篇 |
2021年 | 7篇 |
2020年 | 10篇 |
2019年 | 3篇 |
2018年 | 10篇 |
2017年 | 10篇 |
2016年 | 21篇 |
2015年 | 32篇 |
2014年 | 44篇 |
2013年 | 55篇 |
2012年 | 70篇 |
2011年 | 50篇 |
2010年 | 35篇 |
2009年 | 32篇 |
2008年 | 38篇 |
2007年 | 46篇 |
2006年 | 35篇 |
2005年 | 41篇 |
2004年 | 52篇 |
2003年 | 54篇 |
2002年 | 24篇 |
2001年 | 7篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 7篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1978年 | 4篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 3篇 |
1971年 | 2篇 |
1968年 | 1篇 |
1965年 | 1篇 |
1963年 | 2篇 |
1957年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有783条查询结果,搜索用时 31 毫秒
651.
Helen M. Regan Frank W. Davis Sandy J. Andelman Astrid Widyanata Mariah Freese 《Biodiversity and Conservation》2007,16(9):2715-2728
In this paper we present the results of a multi-criteria decision analysis used to identify a comprehensive set of criteria
for assigning biodiversity value to sites for conservation planning. For effective conservation management, biodiversity value
needs to be a composite of biotic and abiotic factors. However, in the reserve design literature, conservation value is assigned
with a limited set of metrics usually based on comprehensiveness, representativeness and persistence which may be insufficient
at fully capturing biodiversity value. A group of conservation specialists in California, USA, used a multi-criteria decision
making framework to elucidate and weight criteria for scoring biodiversity value at sites. A formal model for consensus and
negotiation was applied to aggregate individuals’ criteria weights across all group members. The group identified ecological
condition, followed by biotic composition as the most important contributors to site conservation value. Long- and short-term
threats causing fragmentation and degradation are also important criteria to consider. Key criteria are identified for which
further data collection would serve the greatest purpose in prioritizing sites and the role of prioritization criteria in
the larger context of systematic conservation planning is discussed. With the recognition that biodiversity value plays an
important role in conservation decisions, the criteria presented here represents a comprehensive suite of factors to consider
when assigning biodiversity value to sites for conservation planning. These can serve as an encompassing list which other
groups can customize for the purpose of biodiversity evaluation for alternative conservation planning contexts. 相似文献
652.
Letavic MA Keith JM Ly KS Barbier AJ Boggs JD Wilson SJ Lord B Lovenberg TW Carruthers NI 《Bioorganic & medicinal chemistry letters》2007,17(9):2566-2569
A series of novel tetrahydronaphthyridine-based histamine H(3) ligands that have serotonin reuptake transporter inhibitor activity is described. The 1,2,3,4-tetrahydro-2,6-naphthyridine scaffold is assembled via the addition of a nitrostyrene to a metalated pyridine followed by reduction and cyclization to form the naphthyridine. In vitro biological data for these novel compounds are discussed. 相似文献
653.
Keith JM Gomez LA Barbier AJ Wilson SJ Boggs JD Lord B Mazur C Aluisio L Lovenberg TW Carruthers NI 《Bioorganic & medicinal chemistry letters》2007,17(15):4374-4377
A series of novel and potent 6-heteroaryl-pyrrolidino-tetrahydroisoquinolines with dual histamine H(3) antagonist/serotonin transporter inhibitor activity is described. In vitro and in vivo data are discussed. 相似文献
654.
This protocol details a method to derive human embryonic stem (hES) cells from single blastomeres. Blastomeres are removed from morula (eight-cell)-stage embryos and cultured until they form multicell aggregates. These blastomere-derived cell aggregates are plated into microdrops seeded with mitotically inactivated feeder cells, and then connected with neighboring microdrops seeded with green fluorescent protein-positive hES cells. The resulting blastomere-derived outgrowths are cultured in the same manner as blastocyst-derived hES cells. The whole process takes about 3-4 months. 相似文献
655.
Pang KS 《Chemico-biological interactions》2009,179(1):45-59
Metabolites arising from chemical entities, old or new, are often mediators of toxicity. Frequently, metabolites are investigated in test animals, with the expectation that the resultant toxicity or activity will mimic the exposure of their formed counterparts. This communication described observations that showed discrepant kinetics between formed and preformed metabolites in the liver, intestine, and kidney, major drug removal organs. Differences in the observed areas under the curve (AUCs) or the extraction ratios (Es) of formed and preformed metabolites in the liver had been attributed to zonal, enzyme heterogeneity, membrane barriers, or transporters. Preformed and formed metabolite also differed in their handling by the kidney; only the preformed and not the formed metabolite would be filtered. In the intestine, differences in the absorption of the precursor and the metabolite and the flow pattern in the intestine would bring about discrepancy in the time-courses of the formed vs. preformed metabolites. Analytical solutions of the AUCs of the metabolites and extraction ratios, based on physiological modeling of the liver, kidney, and intestine, showed that the AUC of the preformed, administered metabolite was dependent only on metabolite parameters, whereas the AUC of the formed metabolite was modulated additionally by the metabolic, secretory and intestinal absorptive intrinsic clearances of the precursor drug. Hence, administration of the synthetic metabolite would not reflect the toxicity associated with the metabolite formed via bioactivation. However, data on preformed metabolite may be used for simultaneous fitting by a combined model of drug and metabolite. Such a strategy is shown to be successful in risk assessment of environmental chemicals. Upon refinement of the resultant model with data on metabolite transport and handling by modeling and simulations, the resultant model would be more robust to provide improved predictions on metabolite toxicity pursuant to drug administration. 相似文献
656.
Iftekhar Bin Naser Yuhong Su Shahidul M. Islam Yohei Shinmyo Sanbing Zhang Giasuddin Ahmed Sandy Chen 《Developmental biology》2009,332(2):351-359
The mesencephalic V neurons and tectobulbar axons in chick embryo project over long distances that appear during the early development of the chick optic tectum. The mesencephalic V neuron and tectobulbar axonal growth begin at Hamburger and Hamilton stage 14 and stage 18, respectively. Both fibers proceed downward from the dorsal to the ventral side of the lateral wall of the optic tectum and then turn caudally and join the medial longitudinal fasciculus. Their axons appear in the most superficial layer of the tectum at early stages and do not cross the dorsal midline of the tectum. Here, we report the role of draxin, a recently identified axon guidance protein, in the formation of the ventrally directed tectum axonal tracts in chicken embryo. draxin is expressed in a high dorsal to low ventral gradient in chick optic tectum. In vitro experiments show that draxin repels neurite outgrowth from dorsal tectum explants. In vivo overexpression resulted in inhibition or misrouting of axon growth in the tectum. Therefore, draxin may be an important member of the collection of repulsive guidance molecules that regulate the formation of the ventrally directed tectum axon tracts. 相似文献
657.
He H Wang Y Guo X Ramchandani S Ma J Shen MF Garcia DA Deng Y Multani AS You MJ Chang S 《Molecular and cellular biology》2009,29(1):229-240
The Protection of telomeres 1 (POT1) protein is a single-stranded telomere binding protein that is essential for proper maintenance of telomere length. Disruption of POT1 function leads to chromosome instability and loss of cellular viability. Here, we show that targeted deletion of the mouse Pot1b gene results in increased apoptosis in highly proliferative tissues. In the setting of telomerase haploinsufficiency, loss of Pot1b results in depletion of germ cells and complete bone marrow failure due to increased apoptosis, culminating in premature death. Pot1b−/− mTR+/− hematopoietic progenitor and stem cells display markedly reduced survival potential in vitro. Accelerated telomere shortening, increased G overhang and elevated number of chromosome end-to-end fusions that initiate an ATR-dependent DNA damage response were also observed. These results indicate an essential role for Pot1b in the maintenance of genome integrity and the long-term viability of proliferative tissues in the setting of telomerase deficiency. Interestingly, these phenotypes closely resemble those found in the human disease dyskeratosis congenita (DC), an inherited syndrome characterized by bone marrow failure, hyperpigmentation, and nail dystrophy. We anticipate that this mouse will serve as a useful model to further understand the pathophysiology of DC. 相似文献
658.
Alfredo Mijares Cilia Abad Sandy Piñero Reinaldo Marín 《Experimental parasitology》2010,124(3):301-305
Trypanosoma evansi is the causative agent of equine trypanosomoses. The disease is characterized by fever, anemia, and cachexia. Peroxidative damage of the red blood cells caused by the parasite, may contribute to the pathogenesis of the anemia seen in trypanosomoses. Consequently, we evaluated the hematocrit, the osmotic fragility of the red blood cells, the level of lipid peroxidation and the activity of the Ca-ATPase of red blood cell ghosts from rats experimentally infected with T. evansi. After 72 h inoculation, the hematocrit decreased from 49.5% to 33%; the osmotic fragility of the red blood cells was approximately 40% higher as compared to the healthy animals; and the red blood cell ghosts showed a higher level of lipid peroxidation and a lower Ca-ATPase activity than the red cell ghosts from the healthy animals. In vitro incubations of red blood cells from healthy animals with T. evansi, produced also a significant increase of the osmotic fragility of the red blood cells. 相似文献
659.
Nora Franceschini V. Saroja Voruganti Karin Haack Laura Almasy Sandy Laston Harald H. H. Göring Jason G. Umans Elisa T. Lee Lyle G. Best Richard R. Fabsitz Jean W. MacCluer Barbara V. Howard Kari E. North Shelley A. Cole 《Human genetics》2010,127(3):295-301
Chronic kidney disease (CKD) is an important public health problem in American Indian populations. Recent research has identified associations of polymorphisms in the myosin heavy chain type II isoform A (MYH9) gene with hypertensive CKD in African-Americans. Whether these associations are also present among American Indian individuals is unknown. To evaluate the role of genetic polymorphisms in the MYH9 gene on kidney disease in American Indians, we genotyped 25 SNPs in the MYH9 gene region in 1,119 comparatively unrelated individuals. Four SNPs failed, and one SNP was monomorphic. We inferred haplotypes using seven SNPs within the region of the previously described E haplotype using Phase v2.1. We studied the association between 20 MYH9 SNPs with kidney function (estimated glomerular filtration rate, eGFR) and CKD (eGFR < 60 ml/min/1.73 m2 or renal replacement therapy or kidney transplant) using age-, sex- and center-adjusted models and measured genotyped within the variance component models. MYH9 SNPs were not significantly associated with kidney traits in additive or recessive genetic adjusted models. MYH9 haplotypes were also not significantly associated with kidney outcomes. In conclusion, common variants in MYH9 polymorphisms may not confer an increased risk of CKD in American Indian populations. Identification of the actual functional genetic variation responsible for the associations seen in African-Americans will likely help to clarify the lack of replication of this gene in our population of American Indians. 相似文献
660.
Shah C McAtee L Breitenbucher JG Rudolph D Li X Lovenberg TW Mazur C Wilson SJ Carruthers NI 《Bioorganic & medicinal chemistry letters》2002,12(22):3309-3312
High throughput screening, using the recombinant human H(3) receptor, was used to identify novel histamine H(3) receptor antagonists. Evaluation of the lead compounds ultimately afforded potent, selective, orally bioavailable compounds (e.g., 38) with favorable blood-brain barrier penetration. 相似文献