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1.
目的观察凉血活血中药对咪喹莫特诱导小鼠银屑病样皮损模型白细胞介素-23/白细胞介素-17(IL-23/IL-17)炎症轴的干预作用。方法 BALB/c雄性小鼠随机分为正常组,模型组,凉血活血中药高、中、低剂量组,采用银屑病皮损严重程度指数(PASI)评分观察银屑病样小鼠模型皮损动态变化;光镜观察皮损组织病理变化;采用酶联免疫法(ELISA)、荧光定量PCR、蛋白免疫印迹分析技术检测小鼠血清及皮损中细胞因子含量、mRNA、蛋白的表达水平。结果凉血活血中药高、中、低剂量组小鼠皮肤红斑的出现、色泽及浸润范围、鳞屑面积、鳞屑厚度、皮肤增厚均小于同期的模型组改变(P0.01或P0.05)。HE染色显示:凉血活血中药组小鼠皮肤表皮层较平整,角化不全的细胞明显减少,表皮层厚度明显低于模型组(P0.01)。皮损蛋白及mRNA检测显示,凉血活血中药组小鼠皮肤中IL-17、IL-23蛋白及IL-23mRNA、IL-22mRNA、孤独核受体γt(RORγt)mRNA表达水平均低于模型组(P0.01或P0.05)。结论凉血活血中药可抑制咪喹莫特诱导的银屑病样炎症爆发的强度及银屑病样皮损的形成,可能与降低IL-23/IL-17轴相关细胞因子蛋白和mRNA表达水平,并抑制Th17细胞分化转录因子RORγt mRNA的表达有关。  相似文献   
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Regulation of hypothalamic–pituitary–adrenocortical (HPA) axis activity by stress is a fundamental survival mechanism and HPA-dysfunction is implicated in psychiatric disorders. Adverse early life experiences, e.g. poor maternal care, negatively influence brain development and programs an abnormal stress response by encoding long-lasting molecular changes, which may extend to the next generation. How HPA-dysfunction leads to the development of affective disorders is complex, but may involve GABAA receptors (GABAARs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABAARs and exhibit stress-protective properties. Importantly, neurosteroid levels rise rapidly during acute stress, are perturbed in chronic stress and are implicated in the behavioural changes associated with early-life adversity. We will appraise how GABAAR-active neurosteroids may impact on HPA axis development and the orchestration of the stress-evoked response. The significance of these actions will be discussed in the context of stress-associated mood disorders.  相似文献   
3.
Gonadotropin releasing hormone (GnRH) neurons originate the nasal placode and migrate into the brain during prenatal development. Once within the brain, these cells become integral components of the hypothalamic–pituitary–gonadal axis, essential for reproductive function. Disruption of this system causes hypogonadotropic hypogonadism (HH). HH associated with anosmia is clinically defined as Kallman syndrome (KS). Recent work examining the developing nasal region has shed new light on cellular composition, cell interactions and molecular cues responsible for the development of this system in different species. This review discusses some developmental aspects, animal models and current advancements in our understanding of pathologies affecting GnRH. In addition we discuss how development of neural crest derivatives such as the glia of the olfactory system and craniofacial structures control GnRH development and reproductive function.  相似文献   
4.
We examined whether the ratio of cortisol (CORT) to high-sensitivity C-reactive protein (hsCRP), an index that captures the integrity of homeostatic regulation between the hypothalamic–pituitary–adrenal (HPA) axis and inflammatory processes, is associated with vulnerability to depression in a gender specific manner and whether glucocorticoid receptor (GR) sensitivity plays a role in these associations. Fasting blood samples were collected between 08:45 and 09:15 and assayed for CORT, hsCRP, and leukocyte count in 213 healthy, medication-free men and women. The NEO-Personality Inventory was used to assess neuroticism, extraversion and anxiety. We used the Hamilton Depression Interview to assess depressive symptoms, the Buss–Perry anger subscale to measure anger, and the Pittsburgh Sleep Quality Index to evaluate subjective sleep quality and its components. Log-transformed CORT/CRP values were analyzed using multiple regression with Holms’ adjusted p-values and age, body mass index (BMI), and race as covariates. GR sensitivity was estimated using the log-transformed ratio of neutrophils (N)-to-monocytes (M). The log-transformed ratio of CORT/CRP did not differ between men and women but was significantly and negatively associated with age and BMI. Severity of depressive symptoms, extraversion, anxiety, and sleep quality were associated with the CORT/CRP ratio in a gender-specific manner. For women, decreasing CORT/CRP ratios, suggestive of an insufficient release of CORT coupled with a heightened inflammatory state, were associated with increasing severity of depressive symptoms, decreasing quality of sleep, increasing frequency of sleep disturbance, and decreasing extraversion. For men, increasing frequency of daytime disturbance and levels of anxiety were associated with increasing CORT/CRP ratio, suggestive of an enhanced release of CORT relative to attenuated levels of hsCRP. For both genders, increasing anger was associated with decreasing CORT/CRP ratios. Although results suggested GR downregulation in women but not men, such differences did not mediate the observed associations. With the use of the CORT/CRP ratio, we showed that vulnerability factors for depression are associated with a loss of normal regulatory controls resulting in gender-specific patterns of neuro-immune dysregulation. That GR downregulation did not influence these associations suggests that the loss of regulatory controls in at risk individuals is primarily at the level of the hormone. Beyond the individual contribution of each component of the CORT/CRP ratio, disruption of normal neuroimmune regulatory feedback provides a plausible biological framework useful in understanding biobehavioral vulnerabilities to depression in a gender specific manner. The CORT/CRP ratio may be a viable biomarker not only for delineating risk for MDD but also progression and treatment responses among patients with MDD; possibilities that are testable in future studies.  相似文献   
5.
目的:以下丘脑-垂体-性腺轴为基础,探究右归丸对肾阳虚大鼠的药理作用,探讨其补肾填精的作用机制。方法:SD大鼠60只,采用氢化可的松建立肾阳虚模型大鼠,随机分为6组,分别为正常组、模型组、甲基睾酮(0.5 g·kg-1)组、右归丸低、中、高剂量组(0.5,1.0,2.5 g·kg-1),每组10只。造模后连续ig给药30 d,分别于给药第15,30天进行强迫负重游泳实验;第30天,眼球取血,放射免疫分析法检测大鼠血清睾酮(testosterone,T)、雌二醇(estradiol,E2)的含量;采用RT-PCR法检测各组大鼠下丘脑、垂体和靶腺(睾丸)钙调蛋白(Ca M)mRNA的表达。结果:与正常组比,模型组大鼠的负重游泳时间减少(P0.05),明显升高血清中E2的激素水平及降低T的激素水平(P0.05),明显升高下丘脑、垂体、睾丸中Ca M mRNA的表达(P0.05);与模型组比,甲基睾酮组、右归丸低、中、高剂量组可明显提高肾阳虚模型大鼠的负重游泳时长(P0.05),给药20 d后其体能趋于正常;给药20 d后甲基睾酮组、右归丸低、中、高剂量组可明显降低血清中E2的激素水平及升高T的激素水平(P0.05),明显降低下丘脑、垂体、睾丸中Ca M mRNA的表达(P0.05)。结论:右归丸可通过调节机体下丘脑-垂体-性腺轴中钙调蛋白基因表达,改善阳虚大鼠激素水平,逆转肾阳虚状态,具有补肾填精的作用。  相似文献   
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Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in the development of ASD and ADHD. Allergic immune reactions, in prenatal and postnatal phases, are examples of these environmental factors, and adverse reactions to foods are reported in these children. In this review, we address the clinical and preclinical findings of (food) allergy in ASD and ADHD and suggest possible underlying mechanisms. Furthermore, opportunities for nutritional interventions in neurodevelopmental disorders are provided.  相似文献   
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中风病发病与肾水亏虚、肝风内动、脑髓气血逆乱等证机有关,三者存在递发关系,“肾-肝-脑”轴失调是中风病核心病机。在经络与功能上,督脉同肾、肝、脑有着密切的联系,针刺督脉腧穴是调节“肾-肝-脑”轴、治疗中风的有效方法。临床及研究证实,百会、大椎穴是治疗中风重要穴位。  相似文献   
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