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81.
Lajić S Clauin S Robins T Vexiau P Blanché H Bellanne-Chantelot C Wedell A 《The Journal of clinical endocrinology and metabolism》2002,87(6):2824-2829
We studied the functional and structural consequences of two novel missense mutations in CYP21 found in women with hyperandrogenism. The women were predicted to carry mutations by hormonal evaluation, but did not display any of the genotypes commonly associated with congenital adrenal hyperplasia. In one woman the novel mutation V304M was found in homozygous form. After expression in COS-1 cells the mutated enzyme was found to have a residual activity of 46% for conversion of 17-hydroxyprogesterone and 26% for conversion of progesterone compared with the normal enzyme. The V304M variant thus represents the sixth known missense mutation associated with nonclassical disease. A normal degradation pattern for this mutant enzyme indicates that the missense mutation is of functional, rather than structural, importance. The other mutation, G375S, was detected in a young woman with signs of hyperandrogenism, in heterozygous form together with P453S, a mutation known to cause nonclassical congenital adrenal hyperplasia (her genotype was G375S+P453S/wild type). This novel variant almost completely abolished enzyme activity; conversion was 1.6% and 0.7% of normal for 17-hydroxyprogesterone and progesterone, respectively. These results underline the importance of genetic evaluation and counseling in hyperandrogenic women who are predicted to carry congenital adrenal hyperplasia-causing mutations by biochemical tests. It also supports the idea that the heterozygous carrier state for CYP21 mutations can be associated with symptoms of androgen excess in certain susceptible individuals. 相似文献
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83.
Elena D. Markova Pyotr A. Slominsky Sergei N. Illarioshkin Natalya I. Miklina Svetlana N. Popova Svetlana A. Limborska Irina A. Ivanova-Smolenskaya 《European journal of neurology》1999,6(5):605-608
We examined a large family of Ashkenazi Jewish origin with autosomal dominant dopa-responsive dystonia (DRD). Mutation analysis of the GTP cyclohydrolase I gene revealed in affected members a novel point mutation (a C/A change in exon 1) resulting in a threonine-to-lysine substitution at residue 94. The mutation was characterized by variable expressivity and was associated with either a 'classical' DRD phenotype or various atypical phenotypes, such as subtle transitory equinovarus postures of the feet or isolated hand tremor. This observation demonstrates the significance of the molecular testing in establishing the clinical diagnosis of DRD. Copyright Lippincott Williams & Wilkins 相似文献
84.
85.
Maria Shadrina Timur Kolomin Tamara Agapova Yan Agniullin Stanislav Shram Petr Slominsky Svetlana Lymborska Nikolay Myasoedov 《Journal of molecular neuroscience : MN》2010,41(1):30-35
Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation, and maintenance of
function of different neuron populations. Some peptides are able to affect the production and activity of neurotrophins. One
of these synthetic peptides is heptapeptide Semax, an analog of the N-terminal adrenocorticotropic hormone fragment 4-10.
It is known that Semax has effects on learning and memory formation and exerts some neuroprotective effects in rodents and
humans. Male Wistar rats were treated for 20 min, 40 min, 90 min, 3 h, 8 h, and 24 h with Semax. Nerve growth factor (NGF)
and brain-derived neurotrophic factor (BDNF) gene expression in rat brain and retina was analyzed by real-time polymerase
chain reaction. It was revealed that after Semax administration the multidirectional activation of the expression of the genes
under investigation in the hippocampus, frontal cortex, and retina was observed. The expression of both neurotrophin genes
was decreased in rat hippocampus and retina 20 min after Semax administration and was increased in the frontal cortex. The
expression levels of NGF remained practically constant in the retina at the initial stage, whereas the expression levels of
BDNF were significantly increased 90 min after Semax administration. 相似文献
86.
87.
Yulia Vistoropsky Svetlana Trofimov Ia Pantsulaia Gregory Livshits 《Annals of human genetics》2006,70(6):749-758
In our research we examined the contribution of putative genetic sources on interindividual variation and cross-sectional correlations of several adhesion molecules, including intracellular (ICAM-1) and vascular cell adhesion molecules (VCAM-1) and E-selectin, in a population-based sample of ethnically homogeneous families of European origin. The plasma levels of these molecules were measured in 947 apparently healthy individuals from 217 nuclear families. Quantitative statistical-genetic analysis implementing the model fitting technique revealed significant parent/offspring and sibling correlations (p < 0.01) for all three molecules. The putative genetic effects explained 55.2 ± 7.2% (VCAM-1), 63.3 ± 7.5% (ICAM) and 63.8 ± 8.1% (E-selectin) of the variation. Common family environmental factors also significantly influenced the variation of E-selectin (13%) and VCAM-1 (28.6%). The main results of our bivariate analysis showed that the observed phenotypic correlations between ICAM-1 and VCAM-1, and between ICAM-1 and E-selectin, were mostly attributable to shared environmental factors ( rE = 0.896 and 0.737, respectively; p < 0.01). However, the correlation between VCAM-1 and E-selectin was likely caused by common genetic effects (rG = 0.334, p < 0.05) . Our results show that familial clustering of adhesion molecules is likely due to strong genetic effects, supplemented with shared environmental factors. 相似文献
88.
SWAP-70-like adapter of T cells,an adapter protein that regulates early TCR-initiated signaling in Th2 lineage cells 总被引:7,自引:0,他引:7
Tanaka Y Bi K Kitamura R Hong S Altman Y Matsumoto A Tabata H Lebedeva S Bushway PJ Altman A 《Immunity》2003,18(3):403-414
We describe the isolation of a protein, SWAP-70-like adapter of T cells (SLAT), which is expressed at high levels in thymocytes and differentiated Th2 cells. SLAT expression was upregulated in differentiating Th2 cells and downregulated in Th1 cells. Ectopic SLAT expression exerted positive or negative effects on IL-4 versus IFNgamma induction, respectively. TCR signaling induced translocation of SLAT to the immunological synapse and its association with ZAP-70 kinase. SLAT reduced the association of ZAP-70 with TCR-zeta and interfered with ZAP-70 but not Lck signaling. Consistent with these results, pharmacological inhibition of ZAP-70 also induced Th2 skewing. Thus, SLAT is a protein which plays a role in Th2 development and/or activation, perhaps by interfering with ZAP-70 signaling. 相似文献
89.
Irene Lambrinoudaki Marc BrincatC. Tamer Erel Marco GambaccianiMette H. Moen Karin Schenck-GustafssonFlorence Tremollieres Svetlana VujovicMargaret Rees Serge Rozenberg 《Maturitas》2010
Introduction
Obesity is a public health problem, with overweight individuals representing approximately 20% of the adult world population. Postmenopausal status is associated with higher prevalence of obesity, as 44% of postmenopausal women are overweight, among whom 23% are obese. Obesity often co-exists with other diseases, the most important being diabetes mellitus, dyslipidemia and hypertension. Furthermore, obesity increases the risk of gynecologic cancer, cardiovascular disease, venous thromboembolism, osteoarthritis and chronic back pain.Aim
To formulate a position statement on the management of the menopause in obese women.Materials and methods
Literature review and consensus of expert opinion.Results and conclusions
Obese women seeking hormone therapy should be evaluated for their individual baseline risk of developing breast cancer, cardiovascular disease and venous thromboembolism. These risks should be weighed against expected benefit from symptom relief, improved quality of life and osteoporosis prevention. The lowest effective estrogen dose should be used (CEE 0.300–0.400 mg or estradiol 0.5–1 mg orally daily or 25–50 μg estradiol transdermally). With regard to progestogens, although no RCT data exist, there are observational studies showing that micronized progesterone or dydrogesterone may have a better risk profile with respect to breast cancer risk. There are no RCT data comparing various progestogens with regard to VTE risk. There are observational data, however, suggesting that micronized progesterone or pregnane derivatives may be associated with a lower VTE risk in postmenopausal women taking HT compared to nonpregnane derivatives. There is a rationale in suggesting the use of transdermal HT in obese women, since this route of administration has been associated with a lesser risk of venous thromboembolism than oral therapy. 相似文献90.
Carlos Rossa Kathryn Ehmann Min Liu Chetan Patil Keith L Kirkwood 《Journal of interferon & cytokine research》2006,26(10):719-729
Coupled bone turnover is directed by the expression of receptor-activated NF-kappaB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Proinflammatory cytokines, such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) induce RANKL expression in bone marrow stromal cells. Here, we report that IL-1beta and TNF-alpha-induced RANKL requires p38 mitogen-activating protein kinase (MAPK) pathway activation for maximal expression. Real-time PCR was used to assess the p38 contribution toward IL-1beta and TNF-alpha-induced RANKL mRNA expression. Steady-state RANKL RNA levels were increased approximately 17-fold by IL-1beta treatment and subsequently reduced approximately 70%-90% when p38 MAPK was inhibited with SB203580. RANKL mRNA stability data indicated that p38 MAPK did not alter the rate of mRNA decay in IL-1beta-induced cells. Using a RANKL-luciferase cell line receptor containing a 120-kB segment of the 5' flanking region of the RANKL gene, reporter expression was stimulated 4-5-fold by IL-1beta or TNF-alpha treatment. IL-1beta-induced RANKL reporter expression was completely blocked with specific p38 inhibitors as well as dominant negative mutant constructs of MAPK kinase-3 and -6. In addition, blocking p38 signaling in bone marrow stromal cells partially inhibited IL-1beta and TNF-alpha-induced osteoclastogenesis in vitro. Results from these studies indicate that p38 MAPK is a major signaling pathway involved in IL-1beta and TNF-alpha-induced RANKL expression in bone marrow stromal cells. 相似文献