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91.
The holy grail of computational tumor modeling is to develop a simulation tool that can be utilized in the clinic to predict neoplastic progression and propose individualized optimal treatment strategies. In order to develop such a predictive model, one must account for many of the complex processes involved in tumor growth. One interaction that has not been incorporated into computational models of neoplastic progression is the impact that organ-imposed physical confinement and heterogeneity have on tumor growth. For this reason, we have taken a cellular automaton algorithm that was originally designed to simulate spherically symmetric tumor growth and generalized the algorithm to incorporate the effects of tissue shape and structure. We show that models that do not account for organ/tissue geometry and topology lead to false conclusions about tumor spread, shape and size. The impact that confinement has on tumor growth is more pronounced when a neoplasm is growing close to, versus far from, the confining boundary. Thus, any clinical simulation tool of cancer progression must not only consider the shape and structure of the organ in which a tumor is growing, but must also consider the location of the tumor within the organ if it is to accurately predict neoplastic growth dynamics. 相似文献
92.
Olsovská J Sulc M Novák P Pazoutová S Flieger M 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2008,873(2):165-172
The UPLC method with diode array UV detection was developed for qualitative determination of ergocristine and ergocristam including degradation products. The mechanism of the ergocristam disruptive reaction was described based on MS/MS characterization of ammonolytic product, N-(d-lysergyl)-l-valinamide (A1) and two methanolytic products, methyl ester of N-(d-lysergyl)-l-valine (M2), and N-[N-(d-lysergyl)-l-valyl]-l-phenylalanyl-d-prolyl methyl ester (M1). The influence of extraction conditions on epimerization and degradation of ergocristine and ergocristam was tested and conditions for reproducible decomposition of ergocristam were found. The presented method could potentially be applied for ergot alkaloids determination in sclerotia, fermentation broth, mycelium, and possibly contaminated food products, i.e. corn, flour, bread, etc., and feeding stuffs containing ungrounded cereals. 相似文献
93.
Functions of nuclear polymeric proteins such as lamin A/C and actin in transport of plasmid DNA were studied. The results show that the lamina plays an important role in plasmid DNA's entry into the cell nucleus from the cytoplasm. Selective disruption of lamin A/C led to a halt in plasmid DNA transport through the nuclear envelope. Inside the nucleus, plasmid DNA was frequently localized at sites with impaired genome integrity, such as DNA double-strand breaks (DSBs), occurring spontaneously or induced by ionizing radiation. Polymeric actin obviously participates in nuclear transport of plasmid DNA, since inhibition of actin polymerization by latrunculin B disturbed plasmid transport inside the cell nucleus. In addition, precluding of actin polymerization inhibited plasmid co-localization with newly induced DSBs. These findings indicate the crucial role of polymeric actin in intranuclear plasmid transport. 相似文献
94.
The latitudinal biodiversity gradient remains one of the most widely recognized yet puzzling patterns in nature [1]. Presently, the high level of extinction of tropical species, referred to as the “tropical biodiversity crisis”, has the potential to erode this pattern. While the connection between species richness, extinction, and speciation has long intrigued biologists [2], [3], these interactions have experienced increased poignancy due to their relevancy to where we should concentrate our conservation efforts. Natural extinction is a phenomenon thought to have its own latitudinal gradient, with lower extinction rates in the tropics being reported in beetles, birds, mammals, and bivalves [4]–[7]. Processes that have buffered ecosystems from high extinction rates in the past may also buffer ecosystems against disturbance of anthropogenic origin. While potential parallels between historical and present-day extinction patterns have been acknowledged, they remain only superficially explored and plant extinction patterns have been particularly neglected. Studies on the disappearances of animal species have reached conflicting conclusions, with the rate of extinction appearing either higher [8] or lower [9] in species richness hotspots. Our global study of extinction risk in vascular plants finds disproportionately higher extinction risk in tropical countries, even when indicators of human pressure (GDP, population density, forest cover change) are taken into account. Our results are at odds with the notion that the tropics represent a museum of plant biodiversity (places of historically lowered extinction) and we discuss mechanisms that may reconcile this apparent contradiction. 相似文献
95.
Background
Infection with high-risk human papillomavirus (HPV)types has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice.Objectives
The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV.Methods
Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2) and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB).Results
Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393) of women were positive for any HPV type by BS-RLB, 18.2% (254/1393) by HR HC2, and 22.3% (310/1393) by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%). HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years.Conclusions
Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future. 相似文献96.
VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis 总被引:4,自引:0,他引:4
Tam BY Wei K Rudge JS Hoffman J Holash J Park SK Yuan J Hefner C Chartier C Lee JS Jiang S Nayak NR Niyak NR Kuypers FA Ma L Sundram U Wu G Garcia JA Schrier SL Maher JJ Johnson RS Yancopoulos GD Mulligan RC Kuo CJ 《Nature medicine》2006,12(7):793-800
Vascular endothelial growth factor (VEGF) exerts crucial functions during pathological angiogenesis and normal physiology. We observed increased hematocrit (60-75%) after high-grade inhibition of VEGF by diverse methods, including adenoviral expression of soluble VEGF receptor (VEGFR) ectodomains, recombinant VEGF Trap protein and the VEGFR2-selective antibody DC101. Increased production of red blood cells (erythrocytosis) occurred in both mouse and primate models, and was associated with near-complete neutralization of VEGF corneal micropocket angiogenesis. High-grade inhibition of VEGF induced hepatic synthesis of erythropoietin (Epo, encoded by Epo) >40-fold through a HIF-1alpha-independent mechanism, in parallel with suppression of renal Epo mRNA. Studies using hepatocyte-specific deletion of the Vegfa gene and hepatocyte-endothelial cell cocultures indicated that blockade of VEGF induced hepatic Epo by interfering with homeostatic VEGFR2-dependent paracrine signaling involving interactions between hepatocytes and endothelial cells. These data indicate that VEGF is a previously unsuspected negative regulator of hepatic Epo synthesis and erythropoiesis and suggest that levels of Epo and erythrocytosis could represent noninvasive surrogate markers for stringent blockade of VEGF in vivo. 相似文献
97.
A gene product of ORF24' was identified on the genome of corynephage BFK20 as a putative phage endolysin. The protein of endolysin BFK20 (gp24') has a modular structure consisting of an N-terminal amidase_2 domain (gp24CD) and a C-terminal cell wall binding domain (gp24BD). The C-terminal domain is unrelated to any of the known cell wall binding domains of phage endolysins. The whole endolysin gene and the sequences of its N-terminal and C-terminal domains were cloned; proteins were expressed in Escherichia coli and purified to homogeneity. The lytic activities of endolysin and its catalytic domain were demonstrated on corynebacteria and bacillus substrates. The binding activity of cell wall binding domain alone and in fusion with green fluorescent protein (gp24BD-GFP) were shown by specific binding assays to the cell surface of BFK20 host Brevibacterium flavum CCM 251 as well as those of other corynebacteria. 相似文献
98.
Penski N Härtle S Rubbenstroth D Krohmann C Ruggli N Schusser B Pfann M Reuter A Gohrbandt S Hundt J Veits J Breithaupt A Kochs G Stech J Summerfield A Vahlenkamp T Kaspers B Staeheli P 《Journal of virology》2011,85(15):7730-7741
From infection studies with cultured chicken cells and experimental mammalian hosts, it is well known that influenza viruses use the nonstructural protein 1 (NS1) to suppress the synthesis of interferon (IFN). However, our current knowledge regarding the in vivo role of virus-encoded NS1 in chickens is much more limited. Here, we report that highly pathogenic avian influenza viruses of subtypes H5N1 and H7N7 lacking fully functional NS1 genes were attenuated in 5-week-old chickens. Surprisingly, in diseased birds infected with NS1 mutants, the IFN levels were not higher than in diseased birds infected with wild-type virus, suggesting that NS1 cannot suppress IFN gene expression in at least one cell population of infected chickens that produces large amounts of the cytokine in vivo. To address the question of why influenza viruses are highly pathogenic in chickens although they strongly activate the innate immune system, we determined whether recombinant chicken alpha interferon (IFN-α) can inhibit the growth of highly pathogenic avian influenza viruses in cultured chicken cells and whether it can ameliorate virus-induced disease in 5-week-old birds. We found that IFN treatment failed to confer substantial protection against challenge with highly pathogenic viruses, although it was effective against viruses with low pathogenic potential. Taken together, our data demonstrate that preventing the synthesis of IFN is not the primary role of the viral NS1 protein during infection of chickens. Our results further suggest that virus-induced IFN does not contribute substantially to resistance of chickens against highly pathogenic influenza viruses. 相似文献
99.
Alexander K Nikodémová M Mária N Kucerová J Jana K Strbák V Vladimír S 《Cellular and molecular neurobiology》2005,25(3-4):681-695
1. Hypophysiotropic thyrotropin-releasing hormone (TRH) is synthesized in the hypothalamic paraventricular nucleus (PVN) and
transported to the median eminence (ME) where it enters the hypophyseal portal blood. TRH in the ME is situated exclusively
in nerve terminals, whereas TRH in the PVN and septum is of extrinsic (nerve terminals) as well as intrinsic (perikarya) origin.
2. To determine the source and possible differential regulation of TRH release from these structures, we blocked TRH axonal
delivery by i.c.v. administration of colchicine into the lateral cerebral ventricle of euthyroid or hypothyroid rats in doses
of 7.5 μg or 7.5, 75 and 100 μg, respectively, two days prior to the evaluation of the TRH secretion from the PVN, ME and
the septum in vitro.
3. In euthyroid rats a low dose of colchicine did not significantly affect plasma TSH. The secretory response to both ethanol
in an isosmolar medium and a high K+ in the ME as well as the PVN explants was well preserved. However, colchicine treatment resulted in the significant increase
of basal secretion of TRH from the PVN.
4. Hypothyroidism induced by 200 mg/l methimazole in drinking water for two weeks resulted in growth arrest, elevated plasma
thyrotropin and decreased TRH content in the PVN and the ME. Colchicine partially decreased elevated plasma thyrotropin and
increased the TRH content in the PVN and its basal release in vitro which was independent of extracellular Ca2+. Interestingly, a TRH release from the PVN could not be further stimulated either by K+ membrane depolarization or by ethanol. TRH responsiveness to the stimulation remained unaffected in the ME. The effect of
colchicine on the septal TRH secretion was intermediate between the effect observed in the PVN and the ME.
5. In conclusion, the absence of a TRH secretory response to stimuli in the PVN after colchicine disruption of the microtubules and Golgi
system suggests that stimulated TRH release observed from the PVN explants in vitro occurs from nerve terminals projecting to the PVN from other brain regions. The independence from extracellular calcium implies
that TRH released under the non-stimulating conditions occurs most likely via the constitutive secretory pathway from dendrites
and/or perikarya. Regulation of septal TRH is markedly different from the hypophysiotropic one.
An erratum to this article is available at . 相似文献
100.
Rebecca S. Williams Jana H. Stollings ?ucja Bundy Regine Haard?rfer Matthew W. Kreuter Patricia Dolan Mullen Mel Hovell Marti Morris Michelle C. Kegler 《PloS one》2016,11(11)
This study examined the extent to which delivery of the minimal Smoke-Free Homes intervention by trained 2-1-1 information and referral specialists had an effect on the adoption of home smoking bans in low-income households. A randomized controlled trial was conducted among 2-1-1 callers (n = 500) assigned to control or intervention conditions. 2-1-1 information and referral specialists collected baseline data and delivered the intervention consisting of 3 mailings and 1 coaching call; university-based data collectors conducted follow-up interviews at 3 and 6 months post-baseline. Data were collected from June 2013 through July 2014. Participants were mostly female (87.2%), African American (61.4%), and smokers (76.6%). Participants assigned to the intervention condition were more likely than controls to report a full ban on smoking in the home at both 3- (38.1% vs 19.3%, p = < .001) and 6-month follow-up (43.2% vs 33.2%, p = .02). The longitudinal intent-to-treat analysis showed a significant intervention effect over time (OR = 1.31, p = .001), i.e. OR = 1.72 at 6 months. This study replicates prior findings showing the effectiveness of the minimal intervention to promote smoke-free homes in low-income households, and extends those findings by demonstrating they can be achieved when 2-1-1 information and referral specialists deliver the intervention. Findings offer support for this intervention as a generalizable and scalable model for reducing secondhand smoke exposure in homes. 相似文献