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971.
Barbara D'haene Catia Attanasio Diane Beysen Jose Dostie Edmond Lemire Philippe Bouchard Michael Field Kristie Jones Birgit Lorenz Bjrn Menten Karen Buysse Filip Pattyn Marc Friedli Catherine Ucla Colette Rossier Carine Wyss Frank Speleman Anne De Paepe Job Dekker Stylianos E. Antonarakis Elfride De Baere 《PLoS genetics》2009,5(6)
To date, the contribution of disrupted potentially cis-regulatory conserved non-coding sequences (CNCs) to human disease is most likely underestimated, as no systematic screens for putative deleterious variations in CNCs have been conducted. As a model for monogenic disease we studied the involvement of genetic changes of CNCs in the cis-regulatory domain of FOXL2 in blepharophimosis syndrome (BPES). Fifty-seven molecularly unsolved BPES patients underwent high-resolution copy number screening and targeted sequencing of CNCs. Apart from three larger distant deletions, a de novo deletion as small as 7.4 kb was found at 283 kb 5′ to FOXL2. The deletion appeared to be triggered by an H-DNA-induced double-stranded break (DSB). In addition, it disrupts a novel long non-coding RNA (ncRNA) PISRT1 and 8 CNCs. The regulatory potential of the deleted CNCs was substantiated by in vitro luciferase assays. Interestingly, Chromosome Conformation Capture (3C) of a 625 kb region surrounding FOXL2 in expressing cellular systems revealed physical interactions of three upstream fragments and the FOXL2 core promoter. Importantly, one of these contains the 7.4 kb deleted fragment. Overall, this study revealed the smallest distant deletion causing monogenic disease and impacts upon the concept of mutation screening in human disease and developmental disorders in particular. 相似文献
972.
Katharine N. Bossart Zhongyu Zhu Deborah Middleton Jessica Klippel Gary Crameri John Bingham Jennifer A. McEachern Diane Green Timothy J. Hancock Yee-Peng Chan Andrew C. Hickey Dimiter S. Dimitrov Lin-Fa Wang Christopher C. Broder 《PLoS pathogens》2009,5(10)
Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID50 within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody. 相似文献
973.
Ventura AK Loken E Mitchell DC Smiciklas-Wright H Birch LL 《Obesity (Silver Spring, Md.)》2006,14(6):1073-1084
Objective: This study describes patterns of bias in self‐reported dietary recall data of girls by examining differences among girls classified as under‐reporters, plausible reporters, and over‐reporters on weight, dietary patterns, and psychosocial characteristics. Research Methods and Procedures: Participants included 176 girls at age 11 and their parents. Girls’ weight and height were measured. Three 24‐hour dietary recalls and responses to psychosocial measures were collected. Plausibility cut‐offs for reported energy intake as a percentage of predicted energy requirements were used to divide the sample into under‐reporters, plausible reporters, and over‐reporters. Differences among these three groups on dietary and psychosocial variables were assessed to examine possible sources of bias in reporting. Results: Using a ±1 standard deviation cut‐off for energy intake plausibility, 50% of the sample was categorized as plausible reporters, 34% as under‐reporters, and 16% as over‐reporters. Weight status of under‐reporters was significantly higher than that of plausible reporters and over‐reporters. With respect to reported dietary intake, under‐reporters were no different from plausible reporters on intakes of foods with higher nutrient densities and lower energy densities and were significantly lower than plausible reporters on intakes of foods with lower nutrient densities and higher energy densities. Over‐reporters reported significantly higher intakes of all food groups and the majority of subgroups, relative to plausible reporters. Under‐reporters had significantly higher levels of weight concern and dietary restraint than both plausible reporters and over‐reporters. Discussion: Techniques to categorize plausible and implausible reporters can and should be used to provide an improved understanding of the nature of error in children's dietary intake data and account for this error in analysis and interpretation. 相似文献
974.
Diane M. Jaworski Paul Soloway John Caterina William A. Falls 《Developmental neurobiology》2006,66(1):82-94
The degradation of the extracellular matrix is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Matrix components of the basement membrane play critical roles in the development and maintenance of the neuromuscular junction (NMJ), yet almost nothing is known about the regulation of MMP and TIMP expression in either the pre‐ or postsynaptic compartments. Here, we demonstrate that TIMP‐2 is expressed by both spinal motor neurons and skeletal muscle. To determine whether motor function is altered in the absence of TIMP‐2, motor behavior was assessed using a battery of tests (e.g., RotaRod, balance beam, hindlimb extension, grip strength, loaded grid, and gait analysis). TIMP‐2?/? mice fall off the RotaRod significantly faster than wild‐type littermates. In addition, hindlimb extension is reduced and gait is both splayed and lengthened in TIMP‐2?/? mice. Motor dysfunction is more pronounced during early postnatal development. A preliminary analysis revealed NMJ alterations in TIMP‐2?/? mice. Juvenile TIMP‐2?/? mice have increased nerve branching and acetylcholine receptor expression. Adult TIMP‐2?/? endplates are enlarged and more complex. This suggests a role for TIMP‐2 in NMJ sculpting during development. In contrast to the increased NMJ nerve branching, cerebellar Purkinje cells have decreased neurite outgrowth. Thus, the TIMP‐2?/? motor phenotype is likely due to both peripheral and central defects. The tissue specificity of the nerve branching phenotype suggests the involvement of different MMPs and/or extracellular matrix molecules underlying the TIMP‐2?/? motor phenotype. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2006 相似文献
975.
Debra A. Schmidt Diane Mulkerin Daniel R. Boehm Mark R. Ellersieck Zhiren Lu Matthew Campbell Tai C. Chen Michael F. Holick 《Zoo biology》2010,29(6):741-752
The purpose of this study was to quantify the ultraviolet B (UVB) output and in vitro previtamin D3 synthesis over time from various artificial light sources. Three incandescent lamps, T‐Rex Active UVHeat 160 watt spot, T‐Rex Active UVHeat 160 watt flood, and ZooMed PowerSun 160 watt flood, and two 1.2 m fluorescent lamps, Sylvania Blacklight 350 BL and ZooMed Reptisun 5.0, were studied. Total UVB irradiance and concentration of previtamin D synthesized using an in vitro ampoule model were quantified initially and at monthly intervals for 1 year. Incandescent lamps were measured at distances of 0.9 and 1.5 m while fluorescent lamps were measured at distances of 30.5 and 45.7 cm at the lamp's center, using both the radiometer and ampoules. Fluorescent lamp irradiance was also measured at the lamp's ends. Data were analyzed as a repeated measures split‐plot in time using SAS with all mean differences determined using Least Squares Means. Incandescent lamp irradiance differences were seen at various distances. The UVHeat lamps had consistently higher previtamin D3 production and irradiance readings compared with the PowerSun lamp. Reptisun 5.0 was consistently higher in UVB irradiance over Sylvania BL 350 at both 30.5 and 45.7 cm. However, there were no differences when comparing conversion of 7‐dehydrocholesterol to previtamin D3. Irradiance differences were detected between the centers and ends of the fluorescent lamps. Until UVB requirements for vitamin D3 synthesis in animals are determined, it is impossible to state that one light is superior to another. Zoo Biol 29:741–752, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
976.
John R. Hadcock David A. Griffith Phillip A. Carpino Shawn C. Black Denise Gautreau Diane M. Hargrove Dennis O. Scott 《Biochemical and biophysical research communications》2010,394(2):366-371
Cannabinoid CB1 receptor antagonists exhibit pharmacologic properties favorable for the treatment of metabolic disease. CP-945,598 (1-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylamino piperidine-4-carboxylic acid amide hydrochloride) is a recently discovered selective, high affinity, competitive CB1 receptor antagonist that inhibits both basal and cannabinoid agonist-mediated CB1 receptor signaling in vitro and in vivo. CP-945,598 exhibits sub-nanomolar potency at human CB1 receptors in both binding (Ki = 0.7 nM) and functional assays (Ki = 0.2 nM). The compound has low affinity (Ki = 7600 nM) for human CB2 receptors. In vivo, CP-945,598 reverses four cannabinoid agonist-mediated CNS-driven responses (hypo-locomotion, hypothermia, analgesia, and catalepsy) to a synthetic cannabinoid receptor agonist. CP-945,598 exhibits dose and concentration-dependent anorectic activity in two models of acute food intake in rodents, fast-induced re-feeding and spontaneous, nocturnal feeding. CP-945,598 also acutely stimulates energy expenditure in rats and decreases the respiratory quotient indicating a metabolic switch to increased fat oxidation. CP-945,598 at 10 mg/kg promoted a 9%, vehicle adjusted weight loss in a 10 day weight loss study in diet-induced obese mice. Concentration/effect relationships combined with ex vivo brain CB1 receptor occupancy data were used to evaluate efficacy in behavioral, food intake, and energy expenditure studies. Together, these in vitro, ex vivo, and in vivo data indicate that CP-945,598 is a novel CB1 receptor competitive antagonist that may further our understanding of the endocannabinoid system. 相似文献
977.
Diversity of Breadfruit (
Artocarpus altilis
, Moraceae) Seasonality: A Resource for Year-Round Nutrition. Breadfruit, Artocarpus altilis (Parkinson) Fosberg, is an important but underutilized staple crop cultivated throughout Oceania and much of the wet tropics.
Indigenous peoples have selected and cultivated cultivars with different fruiting seasons to effectively extend fruit production
for most of the year. In the present study, the seasonality of 219 breadfruit accessions originating from 17 Pacific island
groups, the Seychelles, the Philippines, and Indonesia, and now growing in the National Tropical Botanical Garden’s (NTBG)
Kahanu Garden, Hana, Hawaii, were evaluated. The predominant season of male flower production for most cultivars was from
May to September, and fruit was produced most frequently between August and January. However, there were differences in the
duration of the fruiting season from year to year and among cultivars. Over the 10-year period, 14 cultivars did not reliably
produce fruit; most of this group were ‘ulu afa’ trees collected from Tokelau. About 24 cultivars exhibited very little seasonality
and produced fruit throughout the year. The rest of the cultivars could be clustered into seasonality groups with characteristic
fruiting patterns. Comparison of literature values indicates that unlike Hawaii, the breadfruit season in most locations begins
around the date the sun reaches zenith prior to the summer months and extends throughout the summer months. Five cultivars
asexually propagated from the NTBG collection growing in Kiribati (1°28′ N) exhibit similar fruiting patterns as in Hawaii,
except that they begin 2–3 months earlier. These data predict that cultivars with complementary fruiting seasons in Hawaii
may experience a temporal shift in their seasonality but will maintain their compatibility when cultivated in different locations
and could enable year-round fruit production in many regions. 相似文献
978.
979.
Diane H. Boschelli Joan Subrath Chuansheng Niu Biqi Wu Yan Wang Julie Lee Agnes Brennan Melisa Ho Bijia Deng Xiaoke Yang Xin Xu Louis Leung Jianyao Wang James Atherton Divya Chaudhary 《Bioorganic & medicinal chemistry letters》2010,20(6):1965-1968
Analog 8, a 3-pyridinecarbonitrile with an (E)-2-{6-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl}vinyl group at C-5, had an IC50 value of 1.1 nM for the inhibition of PKCθ and potently blocked the production of IL-2 in both stimulated murine T cells (IC50 = 34 nM) and human whole blood (IC50 = 500 nM). 相似文献