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81.
DNA nucleotide sequence analysis of the immediate-early gene of pseudorabies virus. 总被引:25,自引:4,他引:25 下载免费PDF全文
A K Cheung 《Nucleic acids research》1989,17(12):4637-4646
The complete DNA sequence coding for the immediate-early protein (IE180) of pseudorabies virus was determined. The coding region of IE180 is 4380 nucleotides for 1460 amino acid residues. G+C content of the non-coding portion of the IE gene is 70.3% while the G+C content of the coding portion is considerably higher at 80.1%. Correspondingly, codons consisting mainly of Gs and Cs are favoured. Clusters of amino acid homologies are observed among IE180 of pseudorabies virus, ICP4 of herpes simplex virus type-1 and IE140 of varicella-zoster virus, and are organized similarly in all three polypeptides. Functions exhibited by IE180 are assigned, tentatively, to structural domains of the molecule by analogy to the HSV-1 ICP4 polypeptide. 相似文献
82.
Chu XJ Bartkovitz D Danho W Swistok J Cheung AW Kurylko G Rowan K Yeon M Franco L Qi L Chen L Yagaloff K 《Bioorganic & medicinal chemistry letters》2005,15(22):4910-4914
Linear pentapeptides (Penta-cis-Apc-DPhe-Arg-Trp-Gly-NH2) containing 1-amino-4-phenylcyclohexane-1-carboxylic acid (cis-Apc) and substituted Apc are potent hMC4R agonists and they are inactive or weakly active in hMC1R, hMC3R, and hMC5R agonist assays. This study, together with our earlier report on 5-BrAtc, demonstrated the importance of replacing His6 with phenyl-containing rigid templates in achieving good hMC4R agonist potency and selectivity against hMC1R in linear pentapeptides. 相似文献
83.
The disordered production of inorganic pyrophosphate (PPi) by articular cartilage is thought to have an important role in the pathogenesis of calcium pyrophosphate dihydrate deposition disease and perhaps osteoarthritis. We have previously shown that fetal calf serum added to the culture media of porcine articular cartilage explants increases the elaboration of PPi into the ambient media. We have examined this PPi stimulatory activity by studying the effects of adult human serum (HS), serum derived from adult human plasma (HP), and an acid-alcohol extract of human platelets (PE) on PPi production in cartilage organ culture. Ten percent HS produces a 1.4-fold increase in PPi production after 48 h of culture, while cartilage incubated in media containing 10% HP produces no more PPi than that incubated in media alone. PE stimulates a mean 2-fold increase in PPi production at 48 h in the presence of low concentrations of HP, and has no effect alone. It does not appear to up-regulate the activity of the ectoenzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH), nor does it promote the release of enzyme substrate into the extracellular space. Cartilage exposed to 0.5% HP and PE has 1.51 +/- 0.36 units of NTPPPH activity whereas cartilage exposed to 0.5% HP alone has 1.52 +/- 0.41 units of enzyme activity. PE does not increase the release of [14C]adenine-labeled compounds into the media. Approximately 13% of soluble 14C counts was found in the media of chondrocytes treated with PE while 18% of counts was released in the presence of HP alone. We have demonstrated a factor or factors present in FCS, HS, and an acid-ethanol extract of human platelets which represent(s) the first known physiologic modulators of PPi production in articular cartilage and may increase PPi production without affecting NTPPPH activity. 相似文献
84.
Population‐based analysis of health care contacts among suicide decedents: identifying opportunities for more targeted suicide prevention strategies 下载免费PDF全文
Ayal Schaffer Mark Sinyor Paul Kurdyak Simone Vigod Jitender Sareen Catherine Reis Diane Green James Bolton Anne Rhodes Sophie Grigoriadis John Cairney Amy Cheung 《World psychiatry》2016,15(2):135-145
The objective of this study was to detail the nature and correlates of mental health and non‐mental health care contacts prior to suicide death. We conducted a systematic extraction of data from records at the Office of the Chief Coroner of Ontario of each person who died by suicide in the city of Toronto from 1998 to 2011. Data on 2,835 suicide deaths were linked with provincial health administrative data to identify health care contacts during the 12 months prior to suicide. Sub‐populations of suicide decedents based on the presence and type of mental health care contact were described and compared across socio‐demographic, clinical and suicide‐specific variables. Time periods from last mental health contact to date of death were calculated and a Cox proportional hazards model examined covariates. Among suicide decedents, 91.7% had some type of past‐year health care contact prior to death, 66.4% had a mental health care contact, and 25.3% had only non‐mental health contacts. The most common type of mental health contact was an outpatient primary care visit (54.0%), followed by an outpatient psychiatric visit (39.8%), an emergency department visit (31.1%), and a psychiatric hospitalization (21.0%). The median time from last mental health contact to death was 18 days (interquartile range 5‐63). Mental health contact was significantly associated with female gender, age 25‐64, absence of a psychosocial stressor, diagnosis of schizophrenia or bipolar disorder, past suicide attempt, self‐poisoning method and absence of a suicide note. Significant differences between sub‐populations of suicide decedents based on the presence and nature of their health care contacts suggest the need for targeting of community and clinical‐based suicide prevention strategies. The predominance of ambulatory mental health care contacts, often close to the time of death, reinforce the importance of concentrating efforts on embedding risk assessment and care pathways into all routine primary and specialty clinical care, and not only acute care settings. 相似文献
85.
Dysregulated reactive oxygen species (ROS) generation contributes to many human pathologies, including cancer and diabetes. During normal wound repair, inflammation-induced ROS production must be tightly controlled, but the mechanisms reining their generation remain unclear. Herein, we show that transforming growth factor β-activated kinase 1 (TAK1) directly regulates stem cell factor (SCF) expression, which activates the protein kinase B (PKB)α pro-survival pathway in a cell-autonomous manner to protect keratinocytes from ROS-mediated cell death. TAK1 is a pivotal inflammatory mediator whose expression was transiently elevated during wound healing, paralleling the ROS production profile. TAK1 deficiency in keratinocytes led to increased apoptosis in response to anoikis and TNF-α treatment and was associated with elevated ROS level as analyzed by FACS. Using organotypic skin co-culture and comparative growth factor array analysis, we revealed a cell-autonomous mechanism that involved the SCF/c-Kit/PKBα signaling cascade. Ectopic expression of TAK1 or treatment with exogenous recombinant SCF restored the increased ROS production and apoptotic cell death in TAK1-deficient keratinocytes. Conversely, normal keratinocytes treated with various inhibitors targeting the SCF/c-Kit/PKBα pathway exhibited increased ROS production and TNF-α- or anoikis-induced apoptosis. Our study reveals a novel anti-apoptotic role for SCF in keratinocytes and identifies TAK1 as a novel player uniting inflammation and ROS regulation in skin redox biology. 相似文献
86.
Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population 总被引:6,自引:0,他引:6 下载免费PDF全文
Helgadottir A Gretarsdottir S St Clair D Manolescu A Cheung J Thorleifsson G Pasdar A Grant SF Whalley LJ Hakonarson H Thorsteinsdottir U Kong A Gulcher J Stefansson K MacLeod MJ 《American journal of human genetics》2005,76(3):505-509
Cardiovascular diseases, including myocardial infarction (MI) and stroke, most often occur on the background of atherosclerosis, a condition attributed to the interactions between multiple genetic and environmental risk factors. We recently reported a linkage and association study of MI and stroke that yielded a genetic variant, HapA, in the gene encoding 5-lipoxygenase-activating protein (ALOX5AP), that associates with both diseases in Iceland. We also described another ALOX5AP variant, HapB, that associates with MI in England. To further assess the contribution of the ALOX5AP variants to cardiovascular diseases in a population outside Iceland, we genotyped seven single-nucleotide polymorphisms that define both HapA and HapB from 450 patients with ischemic stroke and 710 controls from Aberdeenshire, Scotland. The Icelandic at-risk haplotype, HapA, had significantly greater frequency in Scottish patients than in controls. The carrier frequency in patients and controls was 33.4% and 26.4%, respectively, which resulted in a relative risk of 1.36, under the assumption of a multiplicative model (P=.007). We did not detect association between HapB and ischemic stroke in the Scottish cohort. However, we observed that HapB was overrepresented in male patients. This replication of haplotype association with stroke in a population outside Iceland further supports a role for ALOX5AP in cardiovascular diseases. 相似文献
87.
Distance distributions in native and random-coil troponin I from frequency-domain measurements of fluorescence energy transfer 总被引:1,自引:0,他引:1
We used time-dependent fluorescence energy transfer to determine the distribution of donor-to-acceptor distances in native and denatured troponin I(TnI). The single tryptophan residue (Trp 158) of TnI served as the donor (D), and the acceptor (A) was a labeled cysteine residue (Cys 133). The time-dependent intensity decays of the donor were measured by the frequency-domain method from 10 to 320 MHz. The frequency response of the donor emission, in the absence and presence of acceptor, was used to recover the distribution of D to A distances, using an algorithm that accounts for the intrinsic multiexponential decay of the donor. In the native state the D–A distribution is characterized by an average distance of 23 Å and a half-width of 12 Å. Denaturation results in a modest increase in the average distance to 27 Å, and a dramatic increase in half-width to 47 Å. We believe the ability to recover distance distributions will have numerous applications in the characterization of biological macromolecules. 相似文献
88.
C Y Cheung 《Peptides》1988,9(1):107-111
The present study was designed to investigate the presence of VIP in fetal adrenals, to determine the changes in adrenal VIP content associated with maturation, and to explore the factors which regulate fetal adrenal VIP release. Adrenal glands from ovine fetuses at 70 to 140 days gestation were used. Adrenal VIP content, as measured by radioimmunoassay, were low at 70 and 80 days of gestation. This was followed by a rapid increase in VIP content from 80 to 110 days reaching a plateau between 110 and 130 days at levels comparable to that in the adult. A significant fall in adrenal VIP content occurred at 140 days, immediately prior to term. Release of VIP from fetal adrenocortical cells in vitro was significantly elevated by angiotensin II at 10(-5) M, while ACTH had no effect. Acetylcholine at 50 microM and high potassium stimulated fetal adrenal VIP release while norepinephrine did not. These results suggest that the VIP neuronal system in the ovine fetal adrenal matures between 80 and 110 days of gestation. Furthermore, the release of VIP from the fetal adrenocortical cells may be regulated by angiotensin II and cholinergic neurotransmitters. 相似文献
89.
Cognitive schema were used to explain health and illness behaviors among Chinese students. University students in Hong Kong were asked to attribute causes and suggest solutions to five health/mental health problems: Weakness/Fatigue, Tension/ Anxiety, Sleep Difficulty, Hollow/Emptiness, and Headache. The patterns of endorsement on the causal and solution categories used for the five problems were compared using a new asymptotic chi-squared test. The response patterns were found to be significantly different across the five problems. Each problem was attributed to multiple causes including psychological, social, situational, somatic, and existential factors. The intended solutions were often related to the nature of the causal attributions especially when the problems were mild. In lay help-seeking, the Hong Kong students would attempt a variety of self-help measures. However, for professional consultation, the medical doctor would be the primary care professional the students would turn to for most of the problems except in the case of Hollow/Emptiness. 相似文献
90.
Chui Wan Cheung Markus Berger Matthias Finkbeiner 《The International Journal of Life Cycle Assessment》2018,23(1):82-94