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991.
The AIDS epidemic has transformed the importance of cytomegalovirus (CMV) as a pathogen for the adult human central nervous system (CNS). At autopsy, about 25 percent of AIDS cases have cytopathologic evidence of CNS infection by CMV. Since almost nothing is known of the host CNS-viral interactions, we have developed a laboratory model of CMV infection of the brain in the guinea pig. In the present paper, we review the syndromes of CMV infection of the human CNS and compare the neuropathological findings of the opportunistic CMV brain infection in AIDS with the model. Destructive meningoencephalitis, perivascular infiltrates, and subependymal inflammation are found in both, but the glial nodule is the most characteristic feature of each. Thus, we demonstrate that the model faithfully reflects the histopathology of the human disease. Furthermore, since we have found that CNS infection is achieved following systemic infection in the guinea pig, the model recapitulates the sequence of infection in humans. 相似文献
992.
Edward C. Jones-López Soyeon Kim Geisa Fregona Patricia Marques-Rodrigues David Jamil Hadad Lucilia Pereira Dutra Molina Solange Vinhas Nancy Reilly Stephanie Moine Soumitesh Chakravorty Mary Gaeddert Rodrigo Ribeiro-Rodrigues Padmini Salgame Moises Palaci David Alland Jerrold J. Ellner Reynaldo Dietze 《PloS one》2014,9(7)
Rationale
The degree to which tuberculosis (TB) is transmitted between persons is variable. Identifying the factors that contribute to transmission could provide new opportunities for TB control. Transmission is influenced by host, bacterial and environmental factors. However, distinguishing their individual effects is problematic because measures of disease severity are tightly correlated, and assessing the virulence of Mycobacterium tuberculosis isolates is complicated by epidemiological and clinical confounders.Objectives
To overcome these problems, we investigated factors potentially associated with TB transmission within households.Methods
We evaluated patients with smear-positive (≥2+), pulmonary TB and classified M. tuberculosis strains into single nucleotide polymorphism genetic cluster groups (SCG). We recorded index case, household contact, and environmental characteristics and tested contacts with tuberculin skin test (TST) and interferon-gamma release assay. Households were classified as high (≥70% of contacts with TST≥10 mm) and low (≤40%) transmission. We used logistic regression to determine independent predictors.Result
From March 2008 to June 2012, we screened 293 TB patients to enroll 124 index cases and their 731 contacts. There were 23 low and 73 high transmission households. Index case factors associated with high transmission were severity of cough as measured by a visual analog cough scale (VACS) and the Leicester Cough Questionnaire (LCQ), and cavitation on chest radiograph. SCG 3b strains tended to be more prevalent in low (27.3%) than in high (12.5%) transmission households (p = 0.11). In adjusted models, only VACS (p<0.001) remained significant. SCG was associated with bilateral disease on chest radiograph (p = 0.002) and marginally associated with LCQ sores (p = 0.058), with group 3b patients having weaker cough.Conclusions
We found differential transmission among otherwise clinically similar patients with advanced TB disease. We propose that distinct strains may cause differing patterns of cough strength and cavitation in the host leading to diverging infectiousness. Larger studies are needed to verify this hypothesis. 相似文献993.
Diversity and community patterns of macro- and megafauna were compared on the Canadian Beaufort shelf and slope. Faunal sampling collected 247 taxa from 48 stations with box core and trawl gear over the summers of 2009–2011 between 50 and 1,000 m in depth. Of the 80 macrofaunal and 167 megafaunal taxa, 23% were uniques, present at only one station. Rare taxa were found to increase proportional to total taxa richness and differ between the shelf ( 100 m) where they tended to be sparse and the slope where they were relatively abundant. The macrofauna principally comprised polychaetes with nephtyid polychaetes dominant on the shelf and maldanid polychaetes (up to 92% in relative abundance/station) dominant on the slope. The megafauna principally comprised echinoderms with Ophiocten sp. (up to 90% in relative abundance/station) dominant on the shelf and Ophiopleura sp. dominant on the slope. Macro- and megafauna had divergent patterns of abundance, taxa richness ( diversity) and diversity. A greater degree of macrofaunal than megafaunal variation in abundance, richness and diversity was explained by confounding factors: location (east-west), sampling year and the timing of sampling with respect to sea-ice conditions. Change in megafaunal abundance, richness and diversity was greatest across the depth gradient, with total abundance and richness elevated on the shelf compared to the slope. We conclude that megafaunal slope taxa were differentiated from shelf taxa, as faunal replacement not nestedness appears to be the main driver of megafaunal diversity across the depth gradient. 相似文献
994.
In biochemical networks, reactions often occur on disparate timescales and can be characterized as either fast or slow. The quasi-steady-state approximation (QSSA) utilizes timescale separation to project models of biochemical networks onto lower-dimensional slow manifolds. As a result, fast elementary reactions are not modeled explicitly, and their effect is captured by nonelementary reaction-rate functions (e.g., Hill functions). The accuracy of the QSSA applied to deterministic systems depends on how well timescales are separated. Recently, it has been proposed to use the nonelementary rate functions obtained via the deterministic QSSA to define propensity functions in stochastic simulations of biochemical networks. In this approach, termed the stochastic QSSA, fast reactions that are part of nonelementary reactions are not simulated, greatly reducing computation time. However, it is unclear when the stochastic QSSA provides an accurate approximation of the original stochastic simulation. We show that, unlike the deterministic QSSA, the validity of the stochastic QSSA does not follow from timescale separation alone, but also depends on the sensitivity of the nonelementary reaction rate functions to changes in the slow species. The stochastic QSSA becomes more accurate when this sensitivity is small. Different types of QSSAs result in nonelementary functions with different sensitivities, and the total QSSA results in less sensitive functions than the standard or the prefactor QSSA. We prove that, as a result, the stochastic QSSA becomes more accurate when nonelementary reaction functions are obtained using the total QSSA. Our work provides an apparently novel condition for the validity of the QSSA in stochastic simulations of biochemical reaction networks with disparate timescales. 相似文献
995.
Ji-Yeon Yu Ji-Hae Kim Tae-Geum Kim Beom-Tae Kim Yong-Suk Jang Jeong-Chae Lee 《Molecules and cells》2010,30(4):303-310
Growing interest in the beneficial effects of antioxidants has inspired the synthesis of new phenolic acid phenethyl ureas
(PAPUs) with enhanced antioxidant potential. We have previously shown the capacity of one PAPU compound, (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea (PAPU1), to induce caspase-dependent apoptosis in melanoma cells. In the present
study, we examined the anti-proliferative effects of PAPU compounds on MCF-7 human breast cancer cells and determined the
molecular mechanisms involved. Treatment with PAPU compounds inhibited predominantly proliferation in these cells, where the
PAPU1 was the most efficient form. Flow cytometric analysis showed that PAPU1 blocked cell cycle progression in the G0/G1 phase, and reduced the proportion of cells in G2/M phase. This was related to the inhibition of cell cycle regulatory factors, including cyclin D/E and cyclin-dependent kinase
(CDK) 2/4, through induction of p21Cip1. PAPU1 also induced the mitochondrial-mediated and caspase-dependent apoptosis in MCF-7 cells. This was evidenced by cellular
changes in the levels of Bcl-2 and Bax, loss of the mitochondrial membrane potential, release of cytochrome c into the cytosol, and caspase-9 activation. Collectively, our results suggest that G1 cell cycle regulatory proteins and mitochondrial pathways are the crucial targets of PAPU1 in the chemoprevention of breast
cancer cells. 相似文献
996.
Bogush TA Dudko EA Beme AA Bogush EA Kim AI Polotsky BE Tjuljandin SA Davydov MI 《Biochemistry. Biokhimii?a》2010,75(12):1421-1427
This review considers data on expression of different types of estrogen receptors (ERα and ERβ) in in vitro cultured cells of non-small cell lung cancer and also in human and animal lung tumors. Estrogens are shown to play an important
role in genesis and development of non-small cell lung cancer because the estrogen-stimulated cell proliferation as well as
antiestrogen-caused inhibition of proliferation occurred only in the cells expressing different types of estrogen receptors.
In general, the situation is similar to that observed in breast cancer, but in the cells of non-small cell lung cancer not
ERα are expressed in more than half of cases but ERβ. Just estrogen receptors β play the crucial role in inducing cell proliferation
in response to estrogens, and ERβ is a prognostic marker of a favorable course of non-small cell lung cancer. Data on the
interactions between ER and EGFR signaling pathways, as well as on the additive antitumor effect of antiestrogens (tamoxifen
and fulvestrant) combined with tyrosine kinase inhibitors (gefitinib, erlotinib, and vandetanib) are considered. The review
also includes data on the influence of estrogens on genesis and development of lung cancer in humans and animals and the frequency
of ERα and ERβ expression in non-small cell lung cancer in tissues from patients of the two sexes. Problems of quantitative
determination of α and β estrogen receptors in the tumor cells are also discussed. 相似文献
997.
Juno Jang Sung-Hwan Hong Dongwon Choi Kang-Seuk Choi Seongman Kang Ik-Hwan Kim 《Applied microbiology and biotechnology》2010,85(5):1509-1520
Newcastle disease virus (NDV) is not only one of the most economically important pathogen of poultry but also has a potential
as anticancer virotherapy. The role of NDV V protein in virus-production kinetics was investigated using DF-1 cell-based production
system. The presence of an anti-interferon (IFN)-alpha antibody resulted in enhanced NDV production kinetics in a dose-dependent
manner by blocking binding of NDV-induced IFN to its receptor. To prepare DF-1 cell whose cellular IFN signaling is blocked
efficiently, stable cell lines expressing either lentogenic or velogenic NDV V protein known as an IFN antagonist were established.
The overexpression of NDV V protein enhanced NDV production kinetics and expedited the rate of NDV production, while it had
no effect on Japanese encephalitis virus production. NDV V protein functions as an IFN antagonist by inhibiting the increase
in type I IFNs by NDV infection. The IFN signals in cells expressing NDV V protein were weakened by decreased activation or
expression of the dsRNA-activated enzymes. These IFN antagonist activities enhance rapid virus replication and spread in the
early phase of viral infection and will be useful in improving the production of viral vaccine strains. 相似文献
998.
Kang Hee-Kwon Jang Jun-Hyuck Shim Jae-Hoon Park Jong-Tae Kim Young-Wan Park Kwan-Hwa 《World journal of microbiology & biotechnology》2010,26(10):1915-1918
4-α-Glucanotransferases possess strong transglycosylation activity which has been used in various carbohydrate chemistry fields.
Due to safety issues of the recombinant enzymes we chose Bacillus subtilis as an expression host to produce a thermostable 4-α-glucanotransferase from Thermus scotoductus (TSαGT). The HpaII promoter in the Gram-positive bacterial vector pUB110 was used first to express TSαGT gene in B. subtilis. However, the activity of TSαGT in B. subtilis was only 4% of that in our previous Escherichia coli system. Two expression systems constructed by sequential alignment of another constitutive promoter for either α-amylase
from B. subtilis NA64 or maltogenic amylase from Bacillus licheniformis downstream of the HpaII promoter elevated the TSαGT productivity by 11- and 12-fold, respectively, compared to the single HpaII promoter system. In conclusion, the dual promoter systems in this study were much better than the single promoter system
to express the TSαGT gene in B. subtilis. 相似文献
999.
Blake C. Ballif Aaron Theisen Ryan N. Traylor Devon Lamb Thrush Caroline Astbury Dennis Bartholomew Kim L. McBride Robert E. Pyatt Kate Shane Wendy E. Smith William B. Gallentine M. Katharine Rudd Julia A. Keene Jean P. Pfotenhauer Pawel Stankiewicz Bassem A. Bejjani 《American journal of human genetics》2010,86(3):454-461
1000.
Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia
Moreno-De-Luca D;SGENE Consortium Mulle JG;Simons Simplex Collection Genetics Consortium Kaminsky EB Sanders SJ;GeneSTAR Myers SM Adam MP Pakula AT Eisenhauer NJ Uhas K Weik L Guy L Care ME Morel CF Boni C Salbert BA Chandrareddy A Demmer LA Chow EW Surti U Aradhya S Pickering DL Golden DM Sanger WG Aston E Brothman AR Gliem TJ Thorland EC Ackley T Iyer R Huang S Barber JC Crolla JA Warren ST Martin CL Ledbetter DH 《American journal of human genetics》2010,87(5):618-630
Autism spectrum disorders (ASD) and schizophrenia are neurodevelopmental disorders for which recent evidence indicates an important etiologic role for rare copy number variants (CNVs) and suggests common genetic mechanisms. We performed cytogenomic array analysis in a discovery sample of patients with neurodevelopmental disorders referred for clinical testing. We detected a recurrent 1.4 Mb deletion at 17q12, which harbors HNF1B, the gene responsible for renal cysts and diabetes syndrome (RCAD), in 18/15,749 patients, including several with ASD, but 0/4,519 controls. We identified additional shared phenotypic features among nine patients available for clinical assessment, including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. In a large follow-up sample, the same deletion was identified in 2/1,182 ASD/neurocognitive impairment and in 4/6,340 schizophrenia patients, but in 0/47,929 controls (corrected p = 7.37 × 10−5). These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function. In addition, the phenotypic features of patients with this CNV are consistent with a contiguous gene syndrome that extends beyond RCAD, which is caused by HNF1B mutations only. 相似文献