全文获取类型
收费全文 | 6601篇 |
免费 | 468篇 |
国内免费 | 41篇 |
专业分类
耳鼻咽喉 | 84篇 |
儿科学 | 248篇 |
妇产科学 | 97篇 |
基础医学 | 957篇 |
口腔科学 | 479篇 |
临床医学 | 640篇 |
内科学 | 1471篇 |
皮肤病学 | 135篇 |
神经病学 | 360篇 |
特种医学 | 566篇 |
外科学 | 580篇 |
综合类 | 44篇 |
一般理论 | 1篇 |
预防医学 | 582篇 |
眼科学 | 98篇 |
药学 | 480篇 |
中国医学 | 69篇 |
肿瘤学 | 219篇 |
出版年
2023年 | 58篇 |
2022年 | 110篇 |
2021年 | 240篇 |
2020年 | 145篇 |
2019年 | 194篇 |
2018年 | 223篇 |
2017年 | 156篇 |
2016年 | 181篇 |
2015年 | 239篇 |
2014年 | 259篇 |
2013年 | 347篇 |
2012年 | 412篇 |
2011年 | 454篇 |
2010年 | 273篇 |
2009年 | 243篇 |
2008年 | 321篇 |
2007年 | 290篇 |
2006年 | 277篇 |
2005年 | 241篇 |
2004年 | 184篇 |
2003年 | 183篇 |
2002年 | 152篇 |
2001年 | 113篇 |
2000年 | 121篇 |
1999年 | 98篇 |
1998年 | 170篇 |
1997年 | 139篇 |
1996年 | 136篇 |
1995年 | 105篇 |
1994年 | 91篇 |
1993年 | 93篇 |
1992年 | 55篇 |
1991年 | 76篇 |
1990年 | 36篇 |
1989年 | 78篇 |
1988年 | 67篇 |
1987年 | 62篇 |
1986年 | 60篇 |
1985年 | 61篇 |
1984年 | 31篇 |
1983年 | 43篇 |
1982年 | 41篇 |
1981年 | 20篇 |
1980年 | 39篇 |
1979年 | 18篇 |
1978年 | 25篇 |
1977年 | 21篇 |
1976年 | 31篇 |
1975年 | 26篇 |
1969年 | 10篇 |
排序方式: 共有7110条查询结果,搜索用时 15 毫秒
41.
C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro 总被引:1,自引:0,他引:1
We have previously shown that activated C1s complement and activated T
cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation
of desLys58 beta2m. This process can specifically be inhibited by
C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously
added desLys58 beta2m in nanomolar amounts to a one-way allogenic mixed
lymphocyte culture (MLC) increased the endogenous production of IL-2 and
the generation of allo-specific cytotoxic T lymphocytes. C1-inh was
purified from fresh human plasma and added to human or murine MLC and
mitogen-stimulated lymphocyte cultures grown in the presence of
complement-inactivated serum. Read-outs were cell proliferation, lymphokine
production and development of T cell-mediated cytotoxicity. We found that
addition of C1-inh to MLC and mitogen- exposed murine and human lymphocyte
cultures inhibited proliferation, the development of allospecific cytotoxic
activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12
and IFN-gamma. These data clearly demonstrate a regulatory function of
C1-inh on T cell- mediated immune functions.
相似文献
42.
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry 总被引:8,自引:1,他引:8
Nistico L; Buzzetti R; Pritchard LE; Van der Auwera B; Giovannini C; Bosi E; Larrad MT; Rios MS; Chow CC; Cockram CS; Jacobs K; Mijovic C; Bain SC; Barnett AH; Vandewalle CL; Schuit F; Gorus FK; Tosi R; Pozzilli P; Todd JA 《Human molecular genetics》1996,5(7):1075-1080
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus
is determined by a combination of environmental and genetic factors, which
include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin
gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2
cannot explain the clustering of type 1 diabetes in families, and a role
for other genes is inferred. In the present report we describe linkage and
association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte
associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong
candidate gene for T cell- mediated autoimmune disease because it encodes a
T cell receptor that mediates T cell apoptosis and is a vital negative
regulator of T cell activation. In addition, we provide supporting evidence
that CTLA-4 is associated with susceptibility to Graves' disease, another
organ- specific autoimmune disease.
相似文献
43.
Burwinkel B; Maichele AJ; Aagenaes O; Bakker HD; Lerner A; Shin YS; Strachan JA; Kilimann MW 《Human molecular genetics》1997,6(7):1109-1115
Glycogen storage disease due to phosphorylase kinase deficiency occurs in
several variants that differ in mode of inheritance and tissue-
specificity. This heterogeneity is suspected to be largely due to mutations
affecting different subunits and isoforms of phosphorylase kinase. The gene
of the ubiquitously expressed beta subunit, PHKB, was a candidate for
involvement in autosomally transmitted phosphorylase kinase deficiency of
liver and muscle. To identify such mutations, the complete PHKB coding
sequence was amplified by RT-PCR of RNA isolated from blood samples of
patients and analyzed by direct sequencing of PCR products. The
characterization of mutations was complemented by PCR of genomic DNA. In
one female and four male patients, we identified five independent nonsense
mutations (Y418ter; R428ter; Y974H+E975ter; Q656ter in two cases), one
single-base insertion in codon N421, one splice-site mutation affecting
exon 31, and a large deletion involving the loss of exon 8. Although these
severe translation-disrupting mutations occur in constitutively expressed
sequences of the only known beta subunit gene of phosphorylase kinase,
PHKB, they are associated with a surprisingly mild clinical phenotype,
affecting virtually only the liver, and relatively high residual enzyme
activity of approximately 10%.
相似文献
44.
Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands 总被引:1,自引:4,他引:1
Smits LJ; Van Poppel FW; Verduin JA; Jongbloet PH; Straatman H; Zielhuis GA 《Human reproduction (Oxford, England)》1997,12(11):2572-2578
The relationship between fecundability and month of birth was investigated
in a cohort of 1526 women who married between 1802 and 1929, using only
women whose first marriage occurred before the age of 35 years. On the
basis of their time to pregnancy (TTP, calculated as time between wedding
and first birth minus gestational length), women were categorized into two
groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348)
and subfecunds (TTP >18 months, n = 118). By use of logistic regression,
cosinor functions with a period of 1 year or 6 months and variable shift
and amplitude were fitted through the monthly odds of subfecunds versus
fecunds. The best fitting curve was unimodal, with a zenith in September (P
= 0.13 for H0: no differences). Exclusion of childless women (n = 36,
minimum follow-up 5 years) from the subfecunds led to a similar curve (P
< 0.01), while childless women, as compared with fecunds, showed a birth
distribution that was best represented with a bimodal curve with zeniths in
January and July (P = 0.06). This study provides evidence for the existence
of differences in fecundability by month of birth. The cause of this
relationship is unclear, but may lie in a melatonin-dependent circannual
variability of the quality of the oocyte.
相似文献
45.
Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism 总被引:3,自引:0,他引:3
Baron J; Winer KK; Yanovski JA; Cunningham AW; Laue L; Zimmerman D; Cutler GB Jr 《Human molecular genetics》1996,5(5):601-606
Parathyroid hormone secretion is negatively regulated by a 7- transmembrane
domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that
activating mutations in this receptor might cause autosomal dominant
hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified,
in two families with ADHP, heterozygous missense mutations in the
Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of
50 normal controls had either mutation. We also identified a de novo,
missense Ca(2+)-sensing receptor mutation in a child with severe sporadic
hypoparathyroidism. The amino acid substitution in one ADHP family affected
the N-terminal, extracellular domain of the receptor. The other mutations
involved the transmembrane region. Unlike patients with acquired
hypoparathyroidism, patients with these mutations had hypercalciuria even
at low serum calcium concentrations. Their greater hypercalciuria
presumably reflected activation of Ca(2+)-sensing receptors in kidney
cells, where the receptor negatively regulates calcium reabsorption. This
augmented hypercalciuria increases the risk of renal complications and thus
has implications for the choice of therapy.
相似文献
46.
R. C. P. Lima-Júnior D. I. M. Sousa G. A. C. Brito G. M. Cunha M. H. Chaves V. S. N. Rao F. A. Santos 《Inflammation research》2007,56(12):487-494
Objective and design: We previously described the visceral antinociceptive property of α, β-amyrin in a mouse model of cystitis induced by cyclophosphamide
(CPM). This study examined the contribution of vanilloid-1 (TRPV1), peripheral NK1 receptors to CPM-evoked nociceptive behaviors
and bladder edema, and its possible modulation by α, β-amyrin.
Methods: The effect of α, β-amyrin (10, 30, and 100 mg/kg, p. o.) and N-acetylcysteine (NAC) on CPM (400 mg/kg, i. p.)-induced cystitis
was studied in mice. Sensory deafferentation was done by a high dose capsaicin. The parameters analysed were: CPM-evoked noxious
behaviors, bladder edema, vascular permeability, and NK1 immunoreactivity. To assess the role of K+
ATP channels in α, β-amyrin effect, animals were pretreated with glibenclamide.
Results: α, β-amyrin (30 and 100 mg/kg) and NAC significantly (p < 0.01) suppressed the visceral pain-related behaviors and NK1 immunoreactivity, but bladder edema was reduced weakly. Glibenclamide reversed the effects of α, β-amyrin. Sensory deafferentation
by capsaicin significantly reduced the nociceptive responses and the NK1 immunoreactivity to noxious stimulation by CPM.
Conclusions: α, β-amyrin attenuates CPM-induced visceral pain and bladder edema by mechanisms that involve, at least in part, a block either
of Substance P release or its receptor function, and partly by opening K+
ATP channels.
Received 13 February 2007; returned for revision 13 April 2007; accepted by G. Geisslinger 14 May 2007 相似文献
47.
Background
Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population. 相似文献48.
Dendritic cells (DCs) can be activated directly by triggering of receptors for pathogens or, indirectly, by exposure to inflammatory signals. It remains unclear, however, whether the two pathways result in qualitatively similar DCs or lead to equivalent adaptive immune responses. Here we report that indirect activation by inflammatory mediators generated DCs that supported CD4(+) T cell clonal expansion but failed to direct T helper cell differentiation. In contrast, exposure to pathogen components resulted in fully activated DCs that promoted T helper responses. These results indicate that inflammation cannot substitute for contact with pathogen components in DC activation and suggest that the function of pattern recognition by DCs is to couple the quality of the adaptive immune response to the nature of the pathogen. 相似文献
49.
Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases 总被引:4,自引:5,他引:4
Preimplantation genetic diagnosis was performed in 61 day 3 embryos
obtained by in-vitro fertilization from seven patient carriers of
haemophilia, Marfan's syndrome, Bloch-Sulzemberg syndrome (incontinentia
pigmentosa) or X chromosome-linked immune deficiency, retinitis pigmentosa,
and FG syndrome, which is characterized by mental retardation and
hypotonia. After multiplex polymerase chain reaction, 16 embryos were
diagnosed as being unaffected, and these were transferred to the uterus on
the following day (day 4). Of these embryos, six (37.5%) implanted,
resulting in the delivery of a singleton and a twin pregnancy, a late
second trimester miscarriage (twins at week 20) and a first trimester
miscarriage at week 8. All the diagnoses were confirmed by amniocentesis.
We report for the first time a late day 4 transfer of biopsied human
embryos undergoing preimplantation genetic diagnosis. This transfer
schedule allows an extra day to perform genetic analyses on single
blastomeres and to monitor any adverse effect of the biopsy procedure.
相似文献
50.