全文获取类型
收费全文 | 170313篇 |
免费 | 14156篇 |
国内免费 | 5818篇 |
专业分类
耳鼻咽喉 | 1146篇 |
儿科学 | 3025篇 |
妇产科学 | 1633篇 |
基础医学 | 26196篇 |
口腔科学 | 3295篇 |
临床医学 | 17026篇 |
内科学 | 22549篇 |
皮肤病学 | 1636篇 |
神经病学 | 8803篇 |
特种医学 | 3360篇 |
外国民族医学 | 29篇 |
外科学 | 13721篇 |
综合类 | 26825篇 |
现状与发展 | 14篇 |
一般理论 | 25篇 |
预防医学 | 11615篇 |
眼科学 | 4493篇 |
药学 | 19201篇 |
33篇 | |
中国医学 | 9422篇 |
肿瘤学 | 16240篇 |
出版年
2024年 | 426篇 |
2023年 | 2289篇 |
2022年 | 4710篇 |
2021年 | 6446篇 |
2020年 | 5836篇 |
2019年 | 5674篇 |
2018年 | 5519篇 |
2017年 | 5555篇 |
2016年 | 5800篇 |
2015年 | 5817篇 |
2014年 | 9236篇 |
2013年 | 10256篇 |
2012年 | 8789篇 |
2011年 | 9900篇 |
2010年 | 8315篇 |
2009年 | 8096篇 |
2008年 | 8031篇 |
2007年 | 8956篇 |
2006年 | 8124篇 |
2005年 | 8127篇 |
2004年 | 7063篇 |
2003年 | 6267篇 |
2002年 | 4597篇 |
2001年 | 4543篇 |
2000年 | 3682篇 |
1999年 | 3444篇 |
1998年 | 2452篇 |
1997年 | 2180篇 |
1996年 | 2276篇 |
1995年 | 2169篇 |
1994年 | 1912篇 |
1993年 | 1749篇 |
1992年 | 1496篇 |
1991年 | 1302篇 |
1990年 | 1082篇 |
1989年 | 1023篇 |
1988年 | 975篇 |
1987年 | 749篇 |
1986年 | 575篇 |
1985年 | 651篇 |
1984年 | 684篇 |
1983年 | 446篇 |
1982年 | 534篇 |
1981年 | 456篇 |
1980年 | 391篇 |
1979年 | 314篇 |
1978年 | 259篇 |
1977年 | 209篇 |
1976年 | 247篇 |
1975年 | 150篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Itoh K Naganawa Y Matsuzawa F Aikawa S Doi H Sasagasako N Yamada T Kira J Kobayashi T Pshezhetsky AV Sakuraba H 《Journal of human genetics》2002,47(1):29-37
Three novel missense mutations in the human lysosomal sialidase gene causing amino acid substitutions (P80L, W240R, and P316S)
in the coding region were identified in two Japanese sialidosis patients. One patient with a severe, congenital form of type
2 sialidosis was a compound heterozygote for 239C-to-T (P80L) and 718T-to-C (W240R). The other patient with a mild juvenile-onset
phenotype (type 1) was a homozygote for the base substitution of 946C-to-T (P316S). None of these mutant cDNA products showed
enzymatic activity toward an artificial substrate when coexpressed in galactosialidosis fibroblastic cells together with protective
protein/cathepsin A (PPCA). All mutants showed a reticular immunofluorescence distribution when coexpressed with the PPCA gene in COS-1 cells, suggesting that the gene products were retained in the endoplasmic reticulum/Golgi area or rapidly degraded
in the lysosomes. Homology modeling of the structural changes introduced by the mutations predicted that the P80L and P316S
transversions cause large conformational changes including the active site residues responsible for binding the sialic acid
carboxylate group. The W240R substitution was deduced to influence the molecular surface structure of a limited region of
the constructed models, which was also influenced by previously identified V217M and G243R transversions.
Received: Stptember 21, 2001 / Accepted: November 2, 2001 相似文献
992.
M Fukuoka K Yasuda H Fujiwara H Kanzaki T Mori 《Human reproduction (Oxford, England)》1992,7(10):1361-1364
We have reported that the cytokines, interleukin-1 (IL-1), tumour necrosis factor alpha (TNF alpha), and interferon (IFN) alpha, beta, and gamma modulate the steroidogenic function of human luteinized granulosa cells in culture. In the present study we examined the interactions between these cytokines in modulating progesterone and oestradiol production by these cells. Neither IL-1 nor TNF alpha had significant effects on human chorionic gonadotrophin (HCG)-stimulated progesterone production, whereas IFN gamma (1-10 ng/ml) significantly reduced HCG-stimulated progesterone production by 26-37%. Concomitant treatment with IL-1 (1 ng/ml) did not further enhance the inhibitory effect of IFN gamma on HCG-stimulated progesterone production. In contrast, the combination of TNF alpha (1 ng/ml) and IFN gamma (10 ng/ml) acted synergistically to markedly inhibit HCG-stimulated progesterone production by 81%. In addition, IL-1 and TNF alpha, neither of which was effective alone, acted synergistically to reduce significantly HCG-stimulated progesterone production by 30%. The combination of TNF alpha and IFN gamma also markedly inhibited follicle stimulating hormone (FSH)-stimulated oestradiol production by 97%, a significantly greater inhibition than that obtained with either cytokine alone. These results suggest that the cytokines may interact to modulate the steroidogenic function of luteal cells in the developing corpus luteum. 相似文献
993.
We have studied the reproducibility of a bronchial leukotriene (LT) provocation test in asthmatics, and the effect of prior treatment with an oral leukotriene D4/E4 antagonist (SR 2640) on LTD4-induced bronchoconstriction in nine asthmatics in a double-blind placebo-controlled randomized cross-over trial. The reproducibility of the bronchial leukotriene provocation test was high. For a specific patient, the replication variance is 0.2303, and the standard deviation is thus 0.4799, corresponding to 48%, i.e. one halving of the dose or half doubling of the dose. SR 2640 antagonised LTD4 induced bronchoconstriction causing a mean shift of 48% to the right of the dose-response curve as compared with placebo (95% confidence interval being 11-137%). This study demonstrates that bronchial LTD4 provocation test is a safe and reproducible method in asthmatics, and that the method can be used to detect LT-antagonism; furthermore that SR 2640 is a weak LTD4-antagonist in asthmatics. 相似文献
994.
Ly-6A/E is a phosphatidylinositol-linked membrane protein which mediates murine T and B cell signalling. IFN-gamma, IFB-alpha/beta, LPS, and IL-4 have all been reported to induce or upregulate Ly-6A/E by normal lymphocytes. Since no systematic study has addressed the stimulant selectivity of Ly-6A/E expression by murine lymphocytes nor investigated its induction and regulation during primary in vivo immune responses we analyzed in vitro Ly-6A/E expression after murine stimuli and during a number of distinct in vivo immunizations. We show that LPS induces B cell Ly-6A/E in vitro by stimulating the release of IFN-alpha/beta by 'contaminating' adherent cells. In the presence of anti-IFN-gamma + anti-IFN-alpha/beta antibodies, no Ly-6A/E was induced upon addition of multiple cytokines, including IL-4, or mitogenic doses of anti-Ig antibody. Furthermore, IFN-gamma-containing, CD4+ T cell (Th1) supernatants potently induced Ly-6A/E by murine B cells whereas IL-4-containing (Th2) supernatants were either weak or ineffective; anti-IFN-gamma + anti-IFN-alpha/beta inhibited Ly-6A/E induction by both Th1 and Th2 supernatants. Immunization of mice with Brucella abortus or poly (I).poly (C) resulted in induction of Ly-6A/E expression by virtually all B and T cells, whereas injection of G alpha M delta led to peak induction of Ly-6A/E by approximately 50% of both B and T cells. Lymphocytes from mice infected with the nematode parasites Nippostrongylus brasiliensis or Heligmosomoides polygyrus expressed no Ly-6A/E.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
995.
H I Abdalla R Baber A Kirkland T Leonard M Power J W Studd 《Human reproduction (Oxford, England)》1990,5(8):1018-1022
Eighty-two patients had 100 cycles of oocyte donation from 68 donors resulting in 27 clinical pregnancies. The source of donated oocytes was 42 fertile volunteers and 26 patients from the assisted conception programme. The pregnancy rate was significantly higher when intra-Fallopian transfer was performed (36%; 21/59), compared with intrauterine transfer (15%; 6/41). The pregnancy rate following fresh gamete/embryo transfer (39%; 15/39) was slightly higher than for frozen embryo transfer (20%; 12/61). The age of the recipient significantly affected the pregnancy rate. The pregnancy rate was 50% in the 25-29 years age group and steadily dropped to 9.7% in the 45-49 age group. The pregnancy rate in patients with primary ovarian failure (50%; 8/16) was significantly higher than in patients with secondary ovarian failure (18%; 9/50). The pregnancy rate was significantly greater when parous donors (33%; 23/69) were used compared with non-parous donors (13%; 4/31). The number of gametes/embryos transferred significantly affected the pregnancy rate regardless of the treatment used. If one or two gametes/embryos were transferred, the pregnancy rate was 11% compared with 33% if three to four embryos were transferred. The age of the donors did not affect the pregnancy rate. The majority of the donors were under the age of 35 years. The best results (50% per cycle) were therefore achieved using gametes from parous donors and transferring three to four oocytes fresh to the Fallopian tubes of a young recipient. 相似文献
996.
Michikawa Y Laderman K Richter K Attardi G 《Somatic Cell and Molecular Genetics》1999,25(5-6):333-342
Previous work had shown a large accumulation (up to 50% of mtDNA) of a noninherited T414G transversion at a critical control site for mtDNA replication in skin fibroblasts from the majority of human subjects above 65 years old, and its absence in younger individuals. In the present studies, long-term in vitro culture of several fibroblasts populations carrying the heteroplasmic T414G mutation revealed an outgrowth of the mutant cells by wild-type cells. This observation supported the previous conclusion that the mutation accumulation is an in vivo phenomenon, while, at the same time, indicating intrinsic physiological differences between mutant and wild-type cells. Furthermore, subcloning experiments revealed a striking mosaic distribution of the mutation in the original fibroblasts populations, as shown by its presence, in heteroplasmic or homoplasmic form, in a fraction (18–32%) of the fibroblasts, and its absence in the others. In other investigations, transfer of mitochondria from mutation-carrying fibroblasts into mtDNA-less 143B.TK–0 206 cells revealed the persistence of the mosaic distribution of the mutation, however, with a near-complete shift to homoplasmy. The generality of the latter phenomenon would exclude a founder effect by one or few mitochondria in the transformation experiments, and would rather point to the important role of the nuclear background in the in vitro behavior of the T414G mutation. The stability of the homoplasmic mutation in 0 cell transformants provides a powerful tool for analyzing its biochemical effects. 相似文献
997.
Summary This study was undertaken to investigate the dose-response relationship between the biological effect and noise exposure, and to consider the mechanism of the appearance of noise effects. Rats were exposed to noise at intensities of 60 dB (A), 80 dB (A) and 100 dB (A) for 240 min and examined for the change of activities of dopamine--hydroxylase (DBH) in serum and adrenal glands. Plasma cyclic adenosine 3,5-monophosphate (c-AMP) levels were also measured. Some rats were given 6-hydroxydopamine (6-OHDA) as a chemical sympathectomyzing agent 20 h before noise exposure in order to consider the mechanism of the appearance of noise effects. By noise exposure, serum DBH activity was significantly (P<0.01) increased at each intensity compared with the control group, but there were no remarkable changes in adrenal DBH activity. Plasma c-AMP level was also significantly elevated in response to the noise stress. When the rats, which had been pretreated with 6-OHDA, were exposed to noise with an intensity of 100 dB (A), the response of serum DBH activity was no longer observed. Therefore it is suggested that the effect due to noise exposure appears through the post-ganglionic sympathetic nerve fiber. 相似文献
998.
Immune-deficient SCID and NOD/SCID mice models as functional assays for studying normal and malignant human hematopoiesis 总被引:3,自引:0,他引:3
T. Lapidot Yfat Fajerman Orit Kollet 《Journal of molecular medicine (Berlin, Germany)》1997,75(9):664-673
Many events and requirements of the developmental program of human hematopoietic stem cells have not yet been discovered.
A major impediment has been the lack of an appropriate experimental system. At present the conditions for maintaining human
stem cells in vitro are not fully known. As a result within a short period the small stem cell pool is lost due to differentiation,
making it difficult to examine the correlation between these cells and their function in vivo. Most of our knowledge of hematopoietic
stem cells is from animal models in which purified stem cell canididates are assayed based on their functional ability to
rescue lethally conditioned recipients. The permanent correction of many genetic disorders of the hematopoietic system requires
efficient methods for introducing genes into stem cells in vitro. However, progress has been hindered by the absence of preclinical
models that assay the repopulating capacity of primitive human cells. In addition, the development of therapy for malignant
diseases also requires assays to identify the target leukemic stem cells based on their ability to initiate the disease. The
recent development of methods to transplant or implant both normal and leukemic cells into immune-deficient mice provides
the foundation for human stem cell assays. These models assay the repopulating capacity of primitive human cells and provide
an important approach to identify and characterize human stem cells, both normal and leukemic. This review focuses on the
development of functional assays for normal and leukemic human stem cells and on the new insights that these models are beginning
to provide on the organization of the human stem cell hierarchy.
Received: 27 January 1997 / Accepted: 3 April 1997 相似文献
999.
F. Rothe G. Wolf 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1994,79(2):400-404
Summary The behaviour of enzymes putatively involved in glutamate/aspartate transmitter metabolism (glutamate dehydrogenase, aspartate aminotransferase, alanine aminotransferase,-glutamyltranspeptidase) was studied in the striatum 3, 7, 14 days and 7 weeks after mechanical destruction of corticostriatal fibres. For a period of up to seven days after unilateral lesion, enzyme activities were significantly diminished (by up to 13% based on protein) in the ipsilateral striatum as compared to the striatum of the intact side. Later, the enzyme activities in the ipsilateral striatum recovered. After seven weeks, an increase was observed for glutamate dehydrogenase activity, whereas the activity of alanine aminotransferase showed a transient rise at the end of the second week. The decrease in enzyme levels is interpreted as being attributable to the destruction of nerve endings which are considered to be glutamatergic, interfering with various compensating processes (e.g. glial cell proliferation) which occur with advancing times after lesion. 相似文献
1000.
Eduard I Dedkov Mathew T Thomas Milan Sonka Fuxing Yang Thomas W Chittenden John M Rhodes Michael Simons Erik L Ritman Robert J Tomanek 《Developmental dynamics》2007,236(7):2004-2010
Syndecan-4 and its cytoplasmic binding partner, synectin, are known to play a role in FGF-2 signaling and vascular growth. To determine their roles in coronary artery/arteriolar formation and growth, we compared syndecan-4 and synectin null mice with their wild-type counterparts. Image analysis of arterioles visualized by smooth muscle alpha-actin immunostaining revealed that synectin (-/-) mice had lower arteriolar length and volume densities than wild-type mice. As shown by electron microscopic analysis, arterioles from the two did not differ in morphology, including their endothelial cell junctions, and the organization and distribution of smooth muscle. Using micro-computer tomography, we found that the size and branching patterns of coronary arteries (diameters > 50 microm) were similar for the two groups, a finding that indicates that the growth of arteries is not influenced by a loss of synectin. Syndecan-4 null male mice also had lower arteriolar length densities than their gender wild-type controls. However, female syndecan-4 null mice were characterized by higher arteriolar length and volume densities than their gender-matched wild-type controls. Thus, we conclude that both synectin and syndecan-4 play a role in arteriolar development, a finding that is consistent with previous evidence that FGF-2 plays a role in coronary arterial growth. Moreover, our data reveal that gender influences the arteriolar growth response to syndecan-4 but not to synectin. 相似文献