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81.
Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10−4 M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle. 相似文献
82.
P E Shapiro 《The American Journal of dermatopathology》1992,14(4):350-356
There is currently much confusion regarding the "dysplastic nevus." There is justification for this confusion, given the abundance of seemingly contradictory statements in the literature. This article proposes a unifying perspective that can help reconcile seemingly contradictory statements and decrease confusion regarding the "dysplastic nevus." The proposed unifying perspective suggests that the "dysplastic nevus" does not exist in nature as a distinct clinical-pathologic entity, but that there is probably legitimacy to the concept of a "dysplastic nevus." 相似文献
83.
84.
New epidemiologic evidence confirming that bias does not explain the aspirin/Reye's syndrome association 总被引:1,自引:0,他引:1
B W Forsyth R I Horwitz D Acampora E D Shapiro C M Viscoli A R Feinstein R Henner N B Holabird B A Jones A D Karabelas 《JAMA》1989,261(17):2517-2524
To determine the validity of the aspirin/Reye's syndrome association, we developed an epidemiologic investigation to assess the effects of five potential sources of bias. A case-control study incorporated procedures to avoid temporal precedence and susceptibility bias. These included classifying cases as having monophasic or biphasic patterns of illness and matching for severity of symptoms at zero-time. To evaluate the effect of a potential recall bias, an "alternate-condition" control group was enrolled. A medical record review study was conducted to assess the potential for diagnostic bias, and a blanket surveillance of all hospitals in a region was conducted to evaluate reporting bias. Twenty-four case subjects and 48 matched controls were enrolled. Eight-eight percent of case subjects and only 17% of controls had received aspirin prior to the onset of Reye's syndrome (matched odds ratio, 35; 95% confidence interval, 4.2 to 288). Further analyses demonstrated that the association could not be attributed to the five potential sources of bias. 相似文献
85.
Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome 总被引:27,自引:0,他引:27
C J Curry R E Magenis M Brown J T Lanman J Tsai P O'Lague P Goodfellow T Mohandas E A Bergner L J Shapiro 《The New England journal of medicine》1984,311(16):1010-1015
We studied two families with an inherited deletion of the short arm of an X chromosome (Xp) in which affected male offspring have epiphyseal stippling in infancy (chondrodysplasia punctata), nasal hypoplasia, ichthyosis, and mental retardation. The presence of ichthyosis and the apparent pattern of X-linked recessive inheritance prompted investigation of the short arm of the X chromosome through studies of genetic markers and focused cytogenetic analysis. Biochemical studies suggested that there was a deletion of three genes previously mapped to the X-chromosome short arm, including the steroid sulfatase locus, the Xg locus, and the M1C2X locus. Prometaphase chromosomes demonstrated a deletion of Xp at p22.32 in the affected boys, in their obligate-carrier mothers, and in 11 of 25 women at risk as potential carriers. The women carrying the Xp deletion had normal gonadal function and fertility but were shorter than the noncarriers in their families (P less than 0.00001). These findings have implications for the genetic organization of this portion of the human X chromosome and demonstrate that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance. 相似文献
86.
Targeted gene disruption of murine CD7 总被引:2,自引:0,他引:2
CD7 is a 40 kDa type I transmembrane glycoprotein member of the Ig
superfamily. CD7 is a marker of mature human T cells and NK cells, and is
expressed early in their development. Cross-linking CD7 positively
modulates T cell and NK cell activity as measured by calcium fluxes,
expression of adhesion molecules, cytokine secretion and proliferation. CD7
associates directly with phosphoinositol 3'-kinase, and CD7 ligation
induces production of D-3 phosphoinositides and tyrosine phosphorylation.
Severe combined immunodeficiency has been associated with a lack of
lymphocyte surface CD7. The CD7 ligand is unknown. The murine CD7 homolog
is encoded by a single gene on chromosome 11. In order to characterize the
role of CD7 in lymphocyte development and function we have eliminated the
CD7 gene by targeted disruption. CD7- deficient mice display normal
histology of thymus and spleen, normal lymphocyte populations in primary
and secondary lymphoid tissues, and normal serum Ig levels. Specific
antibody responses after immunization with T-dependent and T-independent
antigens are equivalent in wild-type and CD7 knockout mice. CD7-deficient
lymphocytes respond normally to T cell mitogenic and allogeneic stimuli,
and display normal NK cell cytotoxicity.
相似文献
87.
Osteogenesis imperfecta (OI) is characterized by fragile bones, skeletal deformity, and growth retardation. This heritable disorder of connective tissue is the result of mutations affecting the COL1A1 and COL1A2 genes of type I collagen. Progress in OI research has been limited because of dependence on human fibroblast and osteoblast specimens and the absence of a naturally occurring animal model for this genetic disorder. Recent technology in molecular biology has led to the development of transgenic models of OI based on site directed mutagenesis of type I collagen genes. OIM is a naturally occurring model which incorporates both the phenotypic and biochemical defects of moderate to severe osteogenesis imperfecta. This powerful tool permits the development of models based on different type I collagen mutations. The collagen type I mutation in OIM is a C propeptide deletion which impairs the production of normal pro-alpha2(I). Tissues in OIM contain only [pro-alpha1(I)]3 homotrimer. Thus, although several animal models are now available for research in osteogenesis imperfecta few are viable or fully mimic human disease disorders. OIM duplicates the phenotype and biochemistry of human disease and has a normal life span. 相似文献
88.
The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity 总被引:20,自引:6,他引:20
Hughes CM; Lewis SE; McKelvey-Martin VJ; Thompson W 《Human reproduction (Oxford, England)》1998,13(5):1240-1247
The integrity of sperm DNA is crucial for the maintenance of genetic
health. A major source of damage is reactive oxygen species (ROS)
generation; therefore, antioxidants may afford protection to sperm DNA. The
objectives of the study were, first, to measure the effects of antioxidant
supplementation in vitro on endogenous DNA damage in spermatozoa using the
single cell gel electrophoresis (comet) assay and, second, to assess the
effect of antioxidant supplementation given prior to X-ray irradiation on
induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll
centrifugation in the presence of ascorbic acid (300, 600 microM), alpha
tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5,
10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand
breakage was measured using the comet assay. Sperm DNA was protected from
DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60
microM) and urate (400 microM). These antioxidants provided protection from
subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or
ascorbate and alpha tocopherol together induced further DNA damage.
Supplementation in vitro with the antioxidants ascorbate, urate and alpha
tocopherol separately has beneficial effects for sperm DNA integrity.
相似文献
89.
OBJECTIVE: We examined sleep, daytime sleepiness and the ability to stay awake during the day in patients affected with retinitis pigmentosa (RP), to further delineate the role of photoreceptors in the circadian cycle. METHODS: Twelve individuals diagnosed with RP (40 +/- 8 years) And 12 normally sighted healthy individuals (39 +/- 7 years) matched for age, body mass index (BMI) and sex were selected for the study. Participants had their sleep recorded on two consecutive nights and were monitored on the two following days. On the first day, their ability to stay awake and on the second, their sleep propensity were assessed using the Maintenance of Wakefulness Test (MWT) and the Multiple Sleep Latency Test (MSLT), respectively. Self-report measures were obtained using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Toronto Hospital Alertness Test (THAT). RESULTS: Subjective daytime sleepiness (ESS: 9 +/- 5 vs. 6 +/- 4, P=0.053) and objectively measured sleep propensity (MSLT: 10 +/- 5 vs. 17 +/- 3 min, P < 0.000) were significantly higher in RP patients than controls, whilst their alertness (THAT: 29 +/- 9 vs. 38 +/- 7, P=0.016) and ability to stay awake (MWT: 21 +/- 9 vs. 29 +/- 2 min, P=0.006) were significantly reduced. Retinitis pigmentosa participants had more disturbed nighttime sleep, with significantly more awakenings (arousal index: 14 +/- 8 vs. 8 +/- 6 h, P=0.039), and tended to have less rapid eye movement (REM) sleep (19 +/- 5 vs. 22 +/- 3%, P=0.094). CONCLUSION: Patients with RP have increased daytime sleepiness, reduced alertness and more disturbed nighttime sleep of poorer quality than their normally sighted counterparts, suggesting an influence of photoreceptor degeneration on the circadian cycle. 相似文献
90.
Cai Guoping Lian Jie Shapiro Sandor S. Beacham Dorothy A. 《Methods in Cell Science》2000,22(2-3):107-114
In this study we introduce a novel in vitro 'oil-drop' assay system for the measurement of endothelial cell (EC) migration, based on the original concept of the Teflon fence assay (Pratt et al., 1984; Am. J. Pathol. 117: 349–354). An aliquot of 15–20,000 human umbilical vein EC (HUVEC) is pipetted through a layer of mineral oil. The cells readily attach, spread and migrate on the surface of a matrix-coated tissue culture dish as a confluent circular monolayer. Migration is measured as the net increase in the total area covered at 24 hours. We have used this system to quantify EC migration on matrices composed of a mixture of type I collagen and either von Willebrand factor (vWF) or fibronectin (FN) in the presence or absence of tumor necrosis factor (TNF). Plating efficiency on both vWF/collagen and FN/collagen, measured by counting cells after attachment and spreading, is about 80%. With this method, migration on vWF/collagen was about 6.4 mm2 and 5.3 mm2 for TNF-treated and untreated HUVEC, respectively. HUVEC migration on FN/collagen was slightly greater – 6.4 mm2 and 6.5 mm2 with and without TNF treatment, respectively. During the 24 hour time period, HUVEC numbers increased 30–40% on vWF/collagen, and 60–80% on FN/collagen, with increased proliferation observed with TNF- treatment. EC proliferation could be completely inhibited by 2 mM hydroxyurea. This assay system has proven useful in our studies to quantify cell migration and proliferation. 相似文献